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Abstract
Cows and ewes fed estrogenic forage may suffer impaired ovarian function, often accompanied by reduced conception rates and increased embryonic loss. Males are relatively unaffected, but the mammary glands in females and castrate males may undergo hypertrophy of the duct epithelium, accompanied by secretion of clear or milky fluid. In cows, clinical signs resemble those associated with cystic ovaries. The infertility is temporary, normally resolving within 1 mo after removal from the estrogenic feed. However, ewes exposed to estrogen for prolonged periods may suffer a second form of infertility that is permanent, caused by developmental actions of estrogen during adult life. The cervix becomes defeminized and loses its ability to store spermatozoa, so conception rates are reduced, although ovarian function remains normal. Importantly, both temporary and permanent infertility in ewes often occur without observable signs and can be detected only by measurement of phytoestrogens in the diet, or measurement of their effects on the animal. Low background concentrations of dietary phytoestrogens are suggested to play an important role in prevention of disease in humans and laboratory rats, but subclinical effects of phytoestrogens in cattle have not yet been described. Effects of low concentrations of phytoestrogens on reproductive function in ruminants are likely to receive increasing attention.
... When animals consume them, these substances can selectively modify Estrogen Receptors (ERs) and function as endocrine disruptors, either mimicking or blocking their activity. The specific effect depends on the amount consumed [5,6]. Hence, they have the potential to disrupt the synthesis, secretion, conveyance, and degradation of reproductive hormones, both in the early stages of growth and in later life. ...
... Hence, they have the potential to disrupt the synthesis, secretion, conveyance, and degradation of reproductive hormones, both in the early stages of growth and in later life. The sources cited are [6,7]. The levels of phytoestrogens in different foods can vary, and this variation can be substantial even among foods in the same category, such as soy beverages and tofu. ...
... The prevalence of is flavone-induced infertility is rising, even in the absence of symptoms. Only the presence of phytoestrogens in the food or their impact on the animal's reproductive efficiency and health may be used to diagnose this illness [6]. Furthermore, long-term soy-containing diet intake by cows has deleterious effects during the first trimester of pregnancy, leading to abortions during the first trimester. ...
The utilization of legumes in animal diets and the adop
... However, the formononetin metabolism leads to the formation of more estrogenic metabolite, which is the chemical equol (Lundh et al., 1990). Metabolic processes catalyzed by microorganisms in the rumen may last six to ten days after ingestion (Adams, 1995). In red clover, biochanin A is the chief estrogen, while formononetin is the inactive estrogen. ...
... Coskun and Izmir (1991) indicated that the reason for such infertility is that spermatozoids experience difficulty in passing into the cervix due to impaired sperm transport function of the cervical mucus during mating and the deterioration in the structure of the cervix. Adams (1995) also reported that especially formononetin and coumestrol cause reproductive abnormalities. Coumestrol, on the other hand, is a potent coumestan that might lower the laying rate of grazing sheep. ...
... Red clover silage retaining isoflavones and alfalfa containing coumestan also result in behavioral anomalies in cows, such as irregular estrus, nymphomania, and anoestrus (Kallela et al., 1984). In this context, by only measuring the phytoestrogens in the diet or monitoring their effects on the reproductive healthiness and fertility of the animals, Adams (1995) asserted that isoflavone-induced infertility could be detected before it even occurs. also reported a decrease in the fertility of heifers fed with berseem clover. ...
... Research has noted a decrease in the ovulation rate and therefore in the frequency of multiple births (Coop and Clark, 1960;Kelly et al, 1980;Ramòn et al, 1993). Reduced conception rates, and increased embryonic loss, have also been reported (Coop and Clark, 1960;Kelly et al, 1980;Shackell and Kelly, 1984;Adams, 1995). In the late 1980s, barren rates in ewes grazing on subterranean clover pastures in Western Australia reached 20% (Adams and Croker, 1987). ...
... The mean decrease in lambs born/ewe in ewes grazing lucerne compared with non-oestrogenic pasture was 10-13% (Coop and Clark, 1960;Reed, 2016). Commonly, cyclicity remains unaffected and no external signs are seen (Adams, 1995), but some reports suggest a lower percentage of ewes being mated during the first cycle period with the rams, Figure 1. Red clover (Trifolium pratense), a perennial legume, that will last 3-5 years. ...
... It is higher in protein content and has greater nitrogen fixing capacity than white clover seen below in Figure 2. suggesting reduced cyclicity (Coop and Clark, 1960;Kelly et al, 1980). This infertility, seen in ewes grazing oestrogenic pastures over tupping, resolves within 1 month of removal from the phytooestrogen source (Adams, 1995). ...
Phyto-oestrogens are plant compounds that mimic the effects of oestrogen. They are mainly found in legumes, especially red and subterranean clover and lucerne. Levels vary with cultivar, season, growing stage and stress to the plant. Consumption of oestrogenic pasture or conserved forage has been shown to have negative effects on reproductive performance of sheep — in particular, a decrease in fecundity and an increase in barren rate. Prolonged exposure may lead to irreversible changes to cervical structure and reproductive performance. Evidence for the impact of phyto-oestrogens on cattle is much weaker than for sheep. The many advantages of clover and lucerne should be exploited, but an understanding of phyto-oestrogenism is needed to avoid unwanted negative impacts on livestock reproductive performance.
... Temporary reversible or potentially permanent infertility can result without any evident signs, and may only be detected through measurement of concentrations within the diet or plasma, or observable by clinical effects [58]. Exposure to a highly estrogenic diet during critical development periods, such as pre-puberty or gonadal maturity, may result in detrimental impacts upon future reproductive functions and fertility in livestock [59]. ...
... In both cows and heifers, many negative reproductive impacts have been recorded, although they are broadly regarded to be a result of phytoestrogens as a collective, rather than focused on coumestans ( Figure 5). These effects include hypertrophy of the duct epithelium, temporary infertility (which is usually resolved after one month from the removal of estrogenic feed), increased secretion of fluid, enlargement of the uterus, nymphomania [44] and other clinical signs resembling cystic ovaries [58]. ...
... Ewes also experience similar negative reproductive effects to those of cattle, however, defeminization of the cervix has been observed in ewes after prolonged exposure to estrogenic feed which results in permanent infertility [58]. Defeminization of the cervix occurs after functional redifferentiation and loss of sexual features [42]. ...
Simple Summary
Phytoestrogens are secondary plant metabolites that play a role in plant defense, and when ingested by livestock have numerous functions related to reproduction, metabolism, immunological functions and livestock growth and performance. Phytoestrogens are found across various plant species, with the most biologically active of these, isoflavones and coumestans, abundant in legume species. Understanding the overall potential health and reproductive effects that may occur in livestock grazing phytoestrogenic pastures is essential to mitigate any potential risks attributed to fertility loss or to introduce proactive management strategies to aid in improving growth and development. A review of their interactions with livestock systems will provide updated information for the agricultural and veterinary industries.
Abstract
Legume crops and pastures have a high economic value in Australia. However, legume species commonly used for grazing enterprises have been identified to produce high concentrations of phytoestrogens. These compounds are heterocyclic phenolic, and are similar in structure to the mammalian estrogen, 17β-estradiol. The biological activity of the various phytoestrogen types; isoflavones, lignans and coumestans, are species-specific, although at concentrations of 25 mg/kg of dry matter each of the phytoestrogen types affect reproductive functions in grazing livestock. The impacts upon fertility in grazing livestock such as cattle and sheep, vary greatly over length of exposure time, age and health of animal and the stress stimuli the plant is exposed to. More recently, research into the other effects that phytoestrogens may have upon metabolism, immune capacity and growth and performance of grazing livestock has been conducted. Potential new benefits for using these phytoestrogens, such as daidzein and genistein, have been identified by observing the stimulation of production in lymphocytes and other antibody cells. Numerous isoflavones have also been recognized to promote protein synthesis, increase the lean meat ratio, and increase weight gain in cattle and sheep. In Australia, the high economic value of legumes as pasture crops in sheep and cattle production enterprises requires proactive management strategies to mitigate risk associated with potential loss of fertility associated with inclusion of pasture legumes as forages for grazing livestock.
... However, the impact of this disease goes way beyond its influence on herbage and seed yield, even when resulting in complete defoliation and premature death of forage plants [2,6,10], as it stimulates the host plants to produce phytoestrogens [2,6,11]. Phytoestrogens affect the ability of plants to resist biotic attack [12], for example, they can provide plants with some protection against fungal and bacterial pathogens [13] and pests [14]. However, phytoestrogens reduce the feed value of the annual Medicago spp. ...
... Of the phytoestrogens, the coumestan coumestrol is a crucial phytoestrogen [21] that can accumulate at high concentrations in Medicago spp. tissues following fungal infection [12,22] or aphid infestation [22]. In addition, environmental conditions affect the phytoestrogen concentration through diverse and complex enzymatic pathways, particularly leading to their accumulation during times of environmental stress [23]. ...
... Despite it being known that higher levels of coumestrol occur in some annual Medicago cultivars during a prolonged dry season [12], in contrast to perennial Medicago spp., studies relating to effects of temperature and/or moisture on coumestrol levels in annual Medicago spp. are lacking. ...
Studies were undertaken to determine the impact of environmental variables temperature (12.5/9.5, 20/17, 27/24 °C day/night) and soil moisture (100, 50% WHC), and their interaction with Phoma medicaginis infection, on production of the phytoestrogen coumestrol in annual Medicago rugosa cv. Paraponto and M. scutellata cv. Sava. Disease factors measured included leaf disease incidence/severity, petiole/stem disease incidence/severity, and leaf yellowing severity. Coumestrol levels were determined using gas chromatography–mass spectrometry (GC–MS). Increasing temperature from 12.5/9.5 °C to 27/24 °C in inoculated plants significantly (p < 0.05) increased coumestrol from 193 mg kg⁻¹ to 390 mg kg⁻¹, but there were no differences in coumestrol production across all three temperatures in uninoculated plants. Reducing soil moisture from 100% to 50% WHC at the highest temperature (27/24 °C) caused the greatest increase in coumestrol production from 156 to 269 mg kg⁻¹ in inoculated plants. The greatest coumestrol production (600 mg kg⁻¹) was under 27/24 °C/50% WHC for Sava infected with P. medicaginis and least coumestrol (1.6 mg kg⁻¹) was Sava under 20/17 °C/50% WHC in the absence of P. medicaginis. Clearly, situations of higher temperatures in conjunction with lower soil moisture levels cause greatest elevation in coumestrol in the presence of P. medicaginis, levels far exceeding the animal risk threshold of 25 mg kg⁻¹.
... Plant-based feeds are considered a rich source of phytoestrogens (PEs), nonsteroidal polyphenolic compounds derived from plant metabolism with conformational structure similar to 17-β estradiol (E2) (3,5) . When ingested by animals, they can act as selective modulators of estrogen receptors (ERs) and act as endocrine disruptors in an agonistic or antagonistic manner, depending on the dose ingested (5,6) , thus interfering with the synthesis, secretion, transport and metabolism of reproductive hormones, during embryonic development and in adult life (6)(7)(8)(9)(10)(11) . ...
... Plant-based feeds are considered a rich source of phytoestrogens (PEs), nonsteroidal polyphenolic compounds derived from plant metabolism with conformational structure similar to 17-β estradiol (E2) (3,5) . When ingested by animals, they can act as selective modulators of estrogen receptors (ERs) and act as endocrine disruptors in an agonistic or antagonistic manner, depending on the dose ingested (5,6) , thus interfering with the synthesis, secretion, transport and metabolism of reproductive hormones, during embryonic development and in adult life (6)(7)(8)(9)(10)(11) . ...
... In males, a positive effect on reproduction has been identified when low concentrations of PEs are administered (37) . This has been attributed to the binding of isoflavones to ERs in the hypothalamus, pituitary gland and testicles, thus stimulating spermatogenesis, sperm maturation and gonadal growth (6) . ...
Phytoestrogens (PEs) are chemical compounds from the secondary metabolism of some plants, they have a potential effect on the reproductive parameters of domestic animals, acting as agonists or antagonists of estrogen receptors. The objective of this review is to know the effects produced by a diet rich in PEs on the reproductive physiology of slaughter animals. A systematic review was carried out in two databases using keywords related to the effects produced by the intake of PEs in the diet on the reproduction of animals for slaughter, only controlled studies developed in vivo were considered. Contradictory results were found, on the one hand, the intake of a high content of polyphenolic compounds from different fodders, in the bovine female, was related to the decrease in fertility, presence of abortions and ovarian cysts; on the other hand, the intake of the high content of PEs induced an increase in the semen quality of the males of the species: cattle, sheep and leporids, so these effects can be attributed to the concentration, the type of PEs, sex, species and even the breed of the animal.
... The results showed that although the expression level in the infection group decreased, there was no statistically significant difference ( Fig. 3A) (one-way ANOVA, P ≤ 0.5). Previous studies have shown a negative correlation between the level of estradiol and the reproductive ability of some animals [35,36], while high concentrations of enterolactone were positively associated with improved reproductive success [37]. Rodents have the ability to produce equol. ...
... Despite their low abundance, these taxa may have significant functionality [56]. For example, the Coriobacteriaceae can convert isoflavone genistein into equol [57],, and the level of equol has a negative correlation with the reproductive success of some animals [35,36]. Consistent with this, the present study found a significant increase in equol concentration in the serum of Brandt's voles infected with C. hepatica. ...
Background
Capillaria hepatica, a zoonotic parasite, is present in the population of Brandt’s voles (Lasiopodomys brandtii) and has been a central issue in ecological studies regarding its impact on host populations. Brandt’s voles are known for their extremely high reproductive capacity, and the population explosion of Brandt’s voles have occurred multiple times in the grasslands of Inner Mongolia over the past few decades. However, the mechanisms underlying the population dynamics of Brandt’s voles, particularly in response to C. hepatica infection, remain poorly understood. Given the critical role of the gut microbiota in modulating hormones within the reproductive endocrine system, this study aims to explore how alterations in the gut microbiota influence the host’s population dynamics in response to C. hepatica infection.
Methods
Female Brandt’s voles were inoculated with eggs of infected C. hepatica, and BALB/C mice were used as a control. At the end of the experimental period, cecal contents were collected for 16 S rRNA amplicon sequencing, and the expression levels of reproductive-related hormones were determined using enzyme-linked immunosorbent assay (ELISA).
Results
C. hepatica infection leads to an increased diversity of gut microbiota in Brandt’s voles, with significant changes in microbial composition. The relative abundance of Muribaculaceae and Eubacteriaceae increased significantly, while that of Rikenellaceae and Lachnospiraceae decreased significantly. The expression level of estradiol in the serum of infected Brandt’s voles shows a slight decrease without statistical significance. However, the expression of equol is significantly higher in the infected group compared to the uninfected group, and the expression of enterolactone is significantly lower in the infected group than in the uninfected group.
Conclusions
This study demonstrates that infection with C. hepatica indirectly affect the abundance of specific gut microbiota in Brandt’s voles, which are associated with reproductive hormones. This indirect effect on hormone expression can subsequently impact the reproductive function of the host. By investigating the changes in specific gut microbiota, this study sheds light on the mechanisms through which parasites regulate population fluctuations in Brandt’s voles.
... However, the introduction of new species carries the risk of detrimental effects of novel plant secondary compounds (PSCs) on health and productivity (Revell and Revell 2007;Durmic and Blache 2012). Perhaps the clearest example of this potential problem is the 'clover disease' that disrupted fertility in sheep that were grazing cultivars of Trifolium subterraneum containing a high concentration of phytoestrogens (Adams and Martin 1983;Adams 1995). Consequently, there is considerable interest in testing for the potential effects of PSCs on reproductive performance in ruminants as a 'duty of care' that must be integrated into programs of forage development (Revell and Revell 2007). ...
... There are few data on the concentration of phytoestrogens in follicular fluid of sheep consuming oestrogenic clovers; however, in humans, there is a strong correlation between the blood and follicular fluid concentrations of endocrine disruptors (Petro et al. 2012). These issues are complex because, even for a dietary phytoestrogen, the dose will vary with plant genotype, season and fertiliser practices (Adams 1995). ...
Context
As a ‘duty of care’, it is important to test whether new forage plants for ruminants contain secondary compounds (PSCs) that affect reproductive performance. We have previously observed, a posteriori, that the presence of a methanolic extract of Biserrula pelecinus during maturation of sheep oocytes increased fertilisation rate and blastocyst development. This result needed to be verified a priori and, if the outcome was repeated, we needed to identify the plant secondary metabolite responsible.
Aims
To test whether PSCs from B. pelecinus, when added to the oocyte maturation medium, improve fertilisation rate and blastocyst development; to test whether loliolide is the active molecule produced by B. pelecinus.
Methods
Methanol–chloroform extracts of B. pelecinus were fractionated using rapid silica filtration and solvents of increasing polarity. Fractions at final concentrations of 0, 100 or 200 μg mL⁻¹ were added to the medium used to mature sheep cumulus–oocyte complexes (COCs) and effects were determined for maturation, subsequent cleavage rate, blastocyst rate, hatching rate, blastocyst efficiency and total blastocyst cell number (TCN).
Results
Fraction BP-6 at 100 μg mL⁻¹ reduced blastocyst rate (P < 0.05), but had no effect when the dose was doubled to 200 μg mL⁻¹. Further fractionation using semi-preparative high-performance liquid chromatography showed loliolide as the most abundant compound in BP-6. Supplementation of the in vitro maturation medium with loliolide (0, 2.5, 5, 10 and 25 μg mL⁻¹) did not affect any measure of embryo development. All COCs treated with B. pelecinus fractions reached the final stage of embryo development, blastocyst hatching. Total blastocyst cell number was not affected.
Conclusion
The presence of fractions of B. pelecinus extract during in vitro oocyte maturation can reduce embryo development.
Implications
In vitro techniques can detect potential effects of forages on reproduction. Some fractions from an extract of B. pelecinus when present during oocyte maturation can reduce embryo development. The abundant PSC, loliolide, was not responsible. There was no indication that a PSC in B. pelecinus improves outcomes.
... Low background concentrations of forage phytoestrogens are believed to play an essential role in disease prevention, but their subclinical effects in cattle have yet to be described. The effects of low concentrations of phytoestrogens on ruminant reproductive function are likely to receive increasing attention (Adams, 1995). ...
... Other plant substances affecting reproductive function are antiestrogens (Schramm et al., 1991;Adams, 1995;Doualla-Bell et al., 1995), antigonadotropins (Shupnik, 1996;Fike et al., 1997;Schneider et al., 2006), antithyroid (Scolari et al., 1962Villar et al., 2002b;Krassas et al., 2010), androgens (Hoffmann & Schuler, 2000;Earl Gray Jr et al., 2006;Akbarinejad et al., 2019). ...
Vitamins are involved in the synthesis of several organic compounds serve as coenzymes. Therefore, they are necessary for different processes such as metabolic regulation, the course of many biochemical reactions, the processes of cellular respiration, the maintenance of acid-base and electrolyte balance, and the protection of cells from oxidative stress. Thus, they support various body functions, including reproductive ones. Consequently, using diets that are not balanced in the composition of micronutrients and, in particular, vitamins can lead to several pathological conditions that affect their reproductive function and the state of the offspring. A deficiency in vitamins often results in reduced enzyme activity. Thus, specific metabolic processes are inhibited, including those in the endocrine glands associated with animal reproduction (such as the pituitary gland, adrenal glands, and ovaries), leading to disruption in the synthesis of gonadotropic and sex hormones. Delayed puberty, disruption of sexual cycles and ovulation, low fertility, and perinatal losses (impaired development and survival of embryos, early death and abortions, osteodystrophy in pregnant women, impaired development and skeletal defects in the fetus, and weak or dead offspring) are registered. Premature births occur, the contractility of the uterus and expulsion of the fetal membranes decreases, and postpartum activity is disturbed. Additionally, the period of manifestation of the first estrus after calving is prolonged, and inflammatory processes such as placentitis, cervicitis, metritis may develop. Moreover, milk fever may occur along with an increase in the frequency of cystic and atrophic ovaries. With excessive or long-term consumption of phytoestrogens, violations of the sexual cycle (from anestrus to nymphomania) can occur. Changes in the structure (cysts or their compaction) and function of the ovaries (synthesis of hormones in the follicles and corpus luteum), hyperemia of the mucous membranes, edema of the reproductive organs and post libido metrorrhagia are observed. Other effects may include prolapse of the vagina, cystic hyperplasia of the endometrium and purulent inflammation of the uterus, the onset of heat during pregnancy, a decrease in the frequency of fertilization, an increase in the loss of embryos, and the death of the fetus, difficult births, a high percentage of stillbirths. Thus, vitamins and biologically active substances of plants significantly impact the reproductive function of animals, so regulating their supply to the body of cows and heifers is an essential factor in ensuring the proper level of herd reproduction.
... The results showed that although the expression level in the infection group decreased, there was no statistically signi cant difference. Previous studies have shown a negative correlation between the level of estradiol and the reproductive ability of some animals [31,32], while high concentrations of enterolactone were positively associated with improved reproductive success [33]. Rodents have the ability to produce estradiol. ...
... Despite their low abundance, these taxa may have signi cant functionality [52]. For example, the Coriobacteriaceae can convert iso avone genistein into equol, [53], and the level of equol has a negative correlation with the reproductive success of some animals [31,32]. ...
Background
Capillaria hepatica, a zoonotic parasite, is present in the population of Brandt's voles (Lasiopodomys brandtii) and has been a central issue in ecological studies regarding its impact on host populations. Brandt's voles are known for their extremely high reproductive capacity, and outbreaks of Brandt's voles have occurred multiple times in the grasslands of Inner Mongolia over the past few decades. However, the mechanisms underlying the population dynamics of Brandt's voles, particularly in response to C. hepatica infection, remain poorly understood. The gut microbiota plays a crucial role in regulating hormones in the reproductive endocrine system. In this study, we investigate the role of gut microbiota in the regulation of host population dynamics in response to C. hepatica infection.
Methods
Female Brandt's voles were inoculated with eggs of infected C. hepatica, and BALB/C mice were used as a control. At the end of the experimental period, cecal contents were collected for 16S rRNA amplicon sequencing, and the expression levels of reproductive-related hormones were determined using enzyme-linked immunosorbent assay (ELISA).
Results
C. hepatica infection leads to an increased diversity of gut microbiota in Brandt's voles, with significant changes in microbial composition. The relative abundance of Muribaculaceae and Eubacteriaceae increased significantly, while that of Rikenellaceae and Lachnospiraceae decreased significantly. The expression level of estradiol in the serum of infected Brandt's voles shows a slight decrease without statistical significance. However, the expression of equol is significantly higher in the infected group compared to the uninfected group, and the expression of enterolactone is significantly lower in the infected group than in the uninfected group.
Conclusions
This study demonstrates that infection with C. hepatica indirectly affect the abundance of gut microbiota in Brandt's voles, which are associated with reproductive hormones. This indirect effect on hormone expression can subsequently impact the reproductive function of the host. By investigating the changes in gut microbiota, this study sheds light on the mechanisms through which parasites regulate population fluctuations in Brandt's voles.
... Bovendien blijkt het effect ook speciesafhankelijk te zijn, waarschijnlijk mee bepaald door de concentratie van natuurlijke oestrogenen in het bloed. Fyto-oestrogenen werken agonistisch bij species met een lage circulerende natuurlijke oestrogeenconcentratie (schapen, rundvee), terwijl species met een relatief hoge circulerende oestrogeenconcentratie, zoals de mens, eerder af te rekenen hebben met antioestrogene effecten van deze fyto-oestrogenen (Adams, 1995). ...
... Zowel bij schapen als koeien verdwenen deze effecten nadat de dieren werden verplaatst naar weiden waarop geen fyto-oestrogeenbevattende planten groeiden. Bij schapen kunnen de gevolgen echter blijvend zijn wanneer ze langer dan drie jaar worden blootgesteld aan deze planten (Adams, 1995). Nutsdieren blijken ook gevoelig te zijn voor zearalenone (Minervini en Dell'Aquila, 2008). ...
... Other herbs, including yucca, turmeric, hops, verbena, yellow dock, and sheep sorrel, contained around 250 ng per g of dried herb. Studies ascribe fertility problems to sheep that consume the phytoestrogen coumestrol found in clover (Adams 1995) and cheetahs given soy-based foods (Setchell et al. 1987). (2011) ...
... /g dried herbSetchell et al. (1987),Adams (1995),Hatcher et al. (2013) Consumer productsShampoos, lipsticks, soaps, and sunscreen Benzophenone-3 (BP3) Variable concentrations Calafat et al. (2008), Krause et al. (2012), Ruszkiewicz et al. (2017) Drinking water and food Drinking water Benzophenone-3 (BP3) n.d. -72 ng/L levels da Silva et al. intake in foods: ∼20-75 ng/day Ericson et al. (2008), Egeghy & Lorber (2011), Gebbink et al. (2015), Shan et al. ...
Concentrations of per and polyfluorinated alkyl substances (PFAS) in drinking water are significantly lower than in vivo levels of the native target hormone. These concentrations are orders of magnitude lower than the hormone in question, particularly when corrected for transactivation. A pregnant woman can excrete about 7,000 μg/day of total estrogens. A low-dose oral contraceptive pill contains 20 μg estradiol. Soy-based baby formula contains phytoestrogens equivalent to a low-dose oral contraceptive pill. A woman on a low-dose oral hormone replacement therapy consumes about 0.5–2 mg/day of one or more estrogens. The levels of endocrine-disrupting substances (EDSs) exposure by oral, respiratory, or dermal routes have the potential to make removing PFAS from drinking water due to its estrogenic activity divert valuable resources. These levels become even less of a threat when their estrogenic potencies are compared with those of the target hormones present as contaminants in water and even more so when compared with levels commonly present in human tissues. The fact that PFAS constitute a tiny fraction compared to exposure to phytoestrogens makes the effort even more insignificant. If PFAS are to be removed from drinking water, it is not due to their estrogenic activity.
HIGHLIGHTS
The levels of EDSs exposure by oral, respiratory, or dermal routes are significant.;
Exposure to estrogenic compounds is primarily through diet, not drinking water.;
PFAS in drinking water typically does not pose a threat due to estrogenic activity. PFAS in drinking water may pose a threat at contaminated sites, warranting remedial action.;
If PFAS is to be removed from drinking water, it is due to toxicity, not estrogenic activity.;
... 대두 가 식품과 사료용으로 널리 이용되는 이유는 훌륭한 단백질 공급원인데 비해 항영양인자, 즉 phytic acid, 올리고 당, 트립신 저해제와 같은 물질이 있어 이러한 물질을 제거하는 필요성이 증가되고 있다 (Dunsford et al., 1989;Li et al., 1990). Phytoestrogen은 양이나 소에 불임을 야기하는 문제가 있고 (Adams, 1995), lectin은 소장에서 영양소 흡 수를 방해하고 (Liener, 1994), phytic acid는 인(P) 과 아연(Z)의 흡수를 떨어뜨린다. 이러한 문제점을 해결하기 위해 FSBM (fermented soybean meal)에 관한 연구가 활발히 진행되고 있다. ...
... A, kefir 60 mL + soybean meal 500 g + water 160 mL; B, kefir 150 mL + soybean meal 500 g + water 70 mL; C, kefir 250 mL + soybean meal 500 g.C는 58%로 C가 가장 높게 나타났는데, 이는 발효대두박의 조합에서 kefir 첨가량이 가장 높은 것에 기인하는 것 으로 판단된다. 대두박의 발효 후 생성되는 특정 아미노산인 histidine, serine, valine, lysine이 증가함에 따라 항산화 효과 증가와 관계가 있다(Adams, 1995). 또한 대두박의 발효 후 증가하는 phenolic 성분들의 농도는 항산화와 금속 chelating 효과를 증가시킨다(Moktan et al., 2008).항염증 ...
... Subsequently, the estrogenic activity of isoflavones sparked controversy regarding their potential benefits. In the 1940s, issues related to breeding difficulties were reported in female sheep grazing on a specific clover variety abundant in isoflavones in Western Australia (Bennetts, Uuderwood, and Shier 1946;Adams 1995;Lundh, Pettersson, and Martinsson 1990). Even in the present day, considerable debate persists regarding the potential impact of consuming soy and soy-based products on fertility (Cooper 2019;Rizzo et al. 2022). ...
In Western countries, the increase in the consumption of soy-derived products raises the population's exposure to isoflavones. These molecules, present in many foods, have numerous effects on the body's cells, including regulation of the transcription and epigenetics, cell signaling, cell cycle, cell growth, apoptosis, and oxidative stress. However, despite the multitude of studies conducted, on these compounds, it remains difficult to draw definitive conclusions regarding their safety or dangerousness in the diet. Indeed, some epidemiological studies highlight health benefits in consuming isoflavone-rich foods, notably by reducing the risk of certain cancers. However, several studies conducted on cell models show that these molecules can have negative effects on cell fate, particularly with regard to proliferation and survival of mammary tumor cells. Isoflavones are mainly genistein, daidzein, formononetin, and biochanin A. These molecules belong to the family of phytoestrogens, which are capable of interacting with both nuclear estrogen receptor, ERα and ERβ, to trigger agonistic and antagonistic effects. Due to their estrogenic properties, isoflavones are suspected to promote hormone-dependent cancers such as breast cancer. This suspicion is based primarily on their ability to bind to ERα in breast cells, thereby altering the signaling pathways that control cell growth. However, study results are sometimes contradictory. Some studies suggest that isoflavones may protect against breast cancer by acting as selective estrogen receptor modulators, while others highlight their potential role in stimulating tumor growth. This review explores the literature on the effects of isoflavones, focusing on their influence on ERα-dependent signaling in breast tumor cells.
... In female sheep, premature chronic exposure to oestrogenic compounds from subterranean clover (Trifolium subterraneum) is linked to delayed onset of puberty [78,79]. ...
The endocrine regulation of mammalian reproductive function is fundamentally governed by the intricate interplay of the sex steroid hormones of the hypothalamic-pituitary-gonadal axis, oestrogens, progestogens and androgens. These hormones are critical in initiating sexual maturation and maintaining reproductive competence throughout an organism’s reproductive life. Ovine models have proven invaluable in elucidating the complexities of sex steroid action in livestock reproduction, with broader implications for our understanding of human reproductive physiology. The exponential growth in our understanding of sex steroids and related reproductive hormones due to improved detection methods of these hormones and production of analogues has significantly improved our capacity to manipulate oestrous cycle events and to exert greater control over reproductive processes. However, several aspects of sex steroid function remain elusive. Notably, the precise nature of neuroendocrine signals that trigger the positive feedback action of estrogen (primarily oestradiol in ovine) in the hypothalamic-pituitary axis remains incompletely characterized. This review synthesizes current knowledge on sex steroid function in reproduction in ovine reproduction, highlighting both advances and persisting knowledge gaps.
... These compounds inhibit enzymes that play a role in steroidogenesis and disrupt the negative feedback of oestrogen by binding to oestrogen receptors in the anterior pituitary or hypothalamus. As a result, they indirectly modify ovarian steroidogenesis (Adams, 1995;Gebrie et al., 2005). ...
... 11 When livestock ingest substantial quantities of forages that are high in phytoestrogens, their reproductive health can be impacted in a variety of ways. 12,13 Additionally, human exposure to phytoestrogens can occur through consumption of plant products containing these phenolic compounds as well as through milk produced by ruminants fed diets rich in phytoestrogens. 14,15 Hence, there is a growing interest in understanding the factors that modulate the concentrations of phytoestrogens in plants fed to dairy animals and other livestock or consumed directly by humans. ...
... Additionally, maternal dystocia can occur due to incomplete dilation of the cervix, particularly when ewes have ingested high levels of isoflavones. Studies have indicated that reduced intake of isoflavones can result in temporary infertility, while prolonged exposure may result in lasting infertility (Marshall, 1973;Adams, 1995;Adams, 1998). ...
Polyphenolic compounds constitute a diverse group of natural components commonly occurring in various plant species, known for their potential to exert both beneficial and detrimental effects. Additionally, these polyphenols have also been implicated as endocrine-disrupting (ED) chemicals, raising concerns about their widespread use in the cosmetics industry. In this comprehensive review, we focus on the body of literature pertaining to the estrogenic properties of ED chemicals, with a particular emphasis on the interaction of isoflavones with estrogen receptors. Within this review, we aim to elucidate the multifaceted roles and effects of polyphenols on the skin, exploring their potential benefits as well as their capacity to act as ED agents. By delving into this intricate subject matter, we intend to provoke thoughtful consideration, effectively opening a Pandora’s box of questions for the reader to ponder. Ultimately, we invite the reader to contemplate whether polyphenols should be regarded as friends or foes in the realm of skincare and endocrine disruption.
... This property was observed in 1940 when Australian ewes feeding on subterranean clover (Trifolium subterraneum L.) showed fertility dysfunctions. Subsequent research on regional cattle forage revealed the estrogenic action of isoflavones, such as formononetin, daidzein, and its metabolite-equol-found in popular clover varieties (Trifolium pretense L. and Trifolium repens L.), which were also linked to reproductive issues in other vertebrates [70,71]. ...
Genistein is a natural compound belonging to flavonoids, having antioxidant, anti-inflammatory, and anti-neoplastic properties. Genistein is considered a phytoestrogen. As such, genistein can bind estrogen receptors (ERα and ERβ), although with a lower affinity than that of estradiol. Despite considerable work, the effects of genistein are not well established yet. This review aims to clarify the role of genistein on female and male reproductive functions in mammals. In females, at a high dose, genistein diminishes the ovarian activity regulating several pathway molecules, such as topoisomerase isoform I and II, protein tyrosine kinases (v-src, Mek-4, ABL, PKC, Syk, EGFR, FGFR), ABC, CFTR, Glut1, Glut4, 5α-reductase, PPAR-γ, mitogen-activated protein kinase A, protein histidine kinase, and recently circulating RNA-miRNA. The effect of genistein on pregnancy is still controversial. In males, genistein exerts an estrogenic effect by inducing testosterone biosynthesis. The interaction of genistein with both natural and synthetic endocrine disruptors has a negative effect on testis function. The positive effect of genistein on sperm quality is still in debate. In conclusion, genistein has a potentially beneficial effect on the mechanisms regulating the reproduction of females and males. However, this is dependent on the dose, the species, the route, and the time of administration.
... Phytoestrogens can both promote and interfere with reproductive processes as reviewed by Sirotkin and Harrath (2014). Thus, it is of interest to study the effect of P. mirifica on cyclic farm animals for reproductive manipulation, as previously mentioned by Adams (1995) as 'effects of low concentrations of phytoestrogens on reproductive function in ruminants are likely to receive increasing attention'. In addition, some phytoestrogens could be involved in the improvement of reproductive performance in goats (Keskin et al., 2004;Al-Hamedawi et al., 2015). ...
... (Bennetts et al., 1946). One study found that sheep that ate a lot of clover had reproductive and fertility problems (Adams, 1995). When cat food was fed a soybean product, cheetahs had lower reproductive rates, but this was reversed when the ingredient was removed from the diet (Sheehan, 1998). ...
Phytoestrogens are plant secondary metabolite that is structurally and functionally similar to mammalian estrogens, which have been shown to have various health benefits in humans. Isoflavones, coumestans, and lignans are the three major bioactive classes of phytoestrogens. It has a complicated mechanism of action involving an interaction with the nuclear estrogen receptor isoforms ERα and ERβ, with estrogen agonist and estrogen antagonist effects. Depending on their concentration and bio-availability in various plant sources, phytoestrogens can act as estrogen agonist or antagonists. Menopausal vasomotor symptoms, breast cancer, cardiovascular disease, prostate cancer, menopausal symptoms, and osteoporosis/bone health have all been studied using phytoestrogens as an additional standard hormone supplemental remedy. The botanical sources, techniques of identification, classification, side effects, clinical implications, pharmacological and therapeutic effects of their proposed mode of action, safety issues, and future directions for phytoestrogens have all been highlighted in this review. K E Y W O R D S coumestans, estrogen, isoflavones, lignans, phytoestrogen
... For this study, bovines were selected as the model, as this species has been the basis for discovery of several factors related to ovarian dynamics in humans. In women, the occurrence of follicular waves, the number of waves during the menstrual cycle, the selection of the dominant follicle and the ovulation of a single follicle are events that are highly similar to those in cows (Adams, 1995;Baerwald, Adams, Pierson, 2003). Ageing in bovines is associated with elevated levels of gonadotrophin and reduced concentrations of steroid hormones, and these changes are consistent with those described during precocious reproductive ageing in women. ...
A basic premise of reproductive physiology is that females have a finite and non-renewable stock of germinative cells, which results in a decrease in reproductive capacity over time. For female bovines, a further factor associated with this decrease is follicular puncture (ovum pickup - OPU), a technique widely used for production of embryos in vitro. As such, it is necessary to seek therapeutic or preventive options for fertility problems, and one potential option is treatment with mesenchymal stem cells (MSC), which exercise a paracrine effect in combating inflammatory and degenerative processes. However, as important as evaluating the efficacy of such treatments is an evaluation of safety. In this context, the current study was carried out with the application of 2.5 x 106 allogenic MSC derived from adipose tissue, to the ovarian cortex of healthy nelore (n = 5) and girolando (n = 5) cows. The animals were subsequently evaluated by ultrasonography, clinical examination, number of viable oocytes collected, and rate of embryo production. None of the animals presented any clinical alteration or any alteration on ultrasonography after receiving the MSC. Furthermore, comparison between the number of viable oocytes, embryos produced, and rate of embryo production before and after MSC application did not show a difference. Based on these data, it can be concluded that intraovarian application of 2.5 x 106 adipose-derived MSC is safe, and this technique represents a potential for study as a therapy in cases of ovarian degeneration or lesions.
... Subclover breeding programs have subsequently aimed to select genotypes with formononetin ≤0.2% of leaf dry matter (Nichols et al. 1996(Nichols et al. , 2013 and no cultivars have been released since 1982 with levels higher than this. Clover disease, previously prevalent across southern Australia, consequently diminished by the 1990s due to adoption of low-formononetin cultivars, as well as improved livestock management (Rossiter 1989;Adams 1995). However, Meat & Livestock Australia reported in 2002 that 10-15 million sheep in the Australian national flock were affected to some level by oestrogenic subclover (Walker et al. 2002) and this likely reflects the persistence of old cultivars of subclover with high levels of formononetin (Foster et al. 2021). ...
The isoflavone formononetin (F) impacts livestock fertility and cultivars of the pasture legume Trifolium subterraneum L. (subclover) have been selected for F levels ≤0.2% of leaf dry weight. However, the impact of waterlogging (WL) on isoflavones is little studied. We investigated the response of isoflavones, biochanin A (BA), genistein (G) and F, to WL for: (1) Yarloop (high F) and eight low F cultivars each from subspecies subterraneum, brachycalycinum and yanninicum (Experiment 1); and (2) four cultivars and 12 ecotypes of ssp. yanninicum (Experiment 2). WL impacted F: estimated means increased from 0.19% (control) to 0.31% (WL) in Experiment 1 and from 0.61% to 0.97% in Experiment 2. Isoflavones under WL were highly heritable, particularly F (H² = 95%). The proportions of BA, G and F were little changed by WL, with strong positive correlations between free-drained and waterlogged treatments. Isoflavone contents were not related to WL tolerance, as assessed by shoot relative growth rate. In conclusion, isoflavones varied among genotypes and increased with WL, but the proportion of individual isoflavones in each genotype was stable. High F under WL was unrelated with genotype tolerance to WL. Instead, it was a consequence of inherently high F for that particular genotype.
... Isoflavones are also called phytoestrogens due to their similar chemical structural to 17-β-estradiol; in fact, they can bind to both estrogen ERα and ERβ receptors, thus exhibiting both estrogenic and antiestrogenic properties [18]. These compounds being estrogenically active were found to be responsible for ewe infertility in Australia [19,20]. Therefore, subterranean clover breeding programs have aimed to select genotypes with low content of the estrogenic isoflavone formononetin [15,21]. ...
Mediterranean pasture and forage legumes are important components of sustainable production systems. Subterranean clover and sulla represent key species having proven high agronomic value and traits for production and multiple services. Our research investigated the potential of the abovementioned species as a source of phenolic compounds and antioxidants for contributing to support their full exploitation in the fodder, animal welfare, and nutraceutical sectors. Antioxidant capacity, as well as the content of total phenolic compounds and individual phenolic compounds, was determined in subterranean clover and sulla shoots at the vegetative, flower bud, flowering, and seed ripening phenological stages. The antioxidant capacity and the phenolic content were affected significantly by harvest time. In subterranean clover, 10 individual phenolic compounds were detected, and isoflavones were the most abundant (3.19–18.27 mg·g⁻¹ DM). Eleven phenolic compounds were identified in sulla shoots, and chlorogenic acid (0.76–3.43 mg·g⁻¹ DM) and diosmin (3.64–4.94 mg·g⁻¹ DM) were the most represented compounds at the vegetative and flower bud stage. On the basis of our findings, a complementary utilization of both legume species is suggested; this might ensure the exploitation of all phenolic compounds in view of the potential benefits for animal production and health.
... Recently, the possibility of genetic harm caused by phytoestrogens was investigated [67] . A recent study found that sheep that consumed a lot of clover experienced infertility and reproductive issues [68] . When fed cat food containing a soybean product, cheetahs had lower reproductive rates, but this was reversed when the ingredient was taken out of the diet [69] . ...
... They also could impair the development of the female genitalia of rodents causing infertility (Nikaido et al., 2004) and implantation losses (Elsayed et al., 2020). Moreover, they were documented to disturb the ovarian function, reduce conception rate as well as upset pregnancy in sheep and cows (Kallela et al., 1984;Adams, 1995). Genistein and daidzein are dominant bioactive members of isoflavones (Šošić-Jurjević et al., 2019). ...
Background: Isoflavones are estrogenic compounds that exist in soy, clover, and peanuts. They are selective estrogen receptor modulators.
Aim: The study was planned to explain the interactions of isoflavones with estrogen receptors alpha (ERα), beta (ERβ), and vascular endothelial growth factor (VEGF) expressions in ovarian and uterine tissues during different stages of the estrous cycle of regular cyclic female Wistar rats.
Methods: Thirty-two regular cyclic females were divided equally into control group: fed casein-based diet and isoflavones group: fed casein-based diet and gavaged 50 mg/kg/day soy isoflavones extract 40%. The regularity of estrus cycles was monitored. Final body weight (FBW), weight gain (BWG), and ovarian and uterine weights were estimated. Histopathology and immunohistochemistry for ERα, Erβ, and VEGF in ovarian and uterine tissues were performed.
Results: All females (100%, n = 16) in control group showed regularity in estrous cycle compared to 62.5% (n = 10) in isoflavones group. Estrus and diestrus phases revealed prolongation and shortening in isoflavones rats than control, respectively. Nonsignificant variation was noted in the duration of the whole cycle of both groups. FBW and BWG significantly decreased however, ovarian and uterine weights increased significantly in all estrous phases of isoflavones group than control. Histopathology demonstrated an increase in number of follicles/ovaries besides, hyperplasia and proliferation of luminal epithelium with hydropic degeneration in the isoflavones group. Also, uterine connective tissue stroma showed edema in the isoflavones group during all estrous phases. Immunostaining percentages of ERα, Erβ, and VEGF protein expression were significantly elevated in the isoflavones group during all estrous phases.
Conclusion: Isoflavones induced irregularity of the estrous cycle that was encountered by increased and altered ERα, Erβ, and VEGF expressions in ovarian and uterine tissues.
... Isoflavones are found almost exclusively in legumes, the soybean and linseed in particular, provide the most abundant source of isoflavones and therefore most soya foods will provide a significant dietary source of these bioactive nonutrients (Reinli and Block, 1996). Isoflavones occur predominantly as glycosides in plants such as red clover and consequently are highly polar (water-soluble) compounds accounts for the low daily intake (Adams, 1995). Two isoflavone molecules, genistein and daidzein, have structures very similar to the body , s natural estrogens. ...
... Phytoestrogens are considered endocrine disruptor compounds (EDCs), as these compounds can alter hormonal effects by stimulating or inhibiting the endocrine system, acting as agonists or antagonists of endogenous steroid hormones, or disturbing the biosynthesis, secretion, transportation, binding, action, degradation or elimination of endogenous hormones that are responsible for the maintenance of homeostasis, reproduction, development and/or behavior [3,4]. Most of the legumes commonly used for feeding livestock or human diets contain anywhere from 5 % to 25 % phytoestrogens, and their concentrations vary depending on the age of the plant, environmental temperature, humidity, light, and pathogens [5]. ...
Phytoestrogens are considered to be endocrine disruptors since they can alter the endocrine system, thus disturbing many reproductive events. The intake of diets containing a high content of phytoestrogens has increased worldwide in human populations and in domestic animals. Phytoestrogens in maternal blood can pass through the placenta to the fetus in high amounts and can have long-term organizational effects. Mesquite (Prosopis sp) is a leguminous plant widely used to feed several livestock species and is also used in the human diet. In this study, we assessed the effects of exposure to mesquite pod extract during the periconception and pregnancy periods on the reproduction of male and female descendants. The females of three experimental groups received one of the following treatments: 1) vehicle injection; 2) mesquite pod extract, or 3) the isoflavone daidzein during the periconception and pregnancy periods. Estrous cyclicity, sexual behavior, and hormones, as well as uterine and vaginal epithelia, were evaluated in the female descendants. In the males, sexual behavior and hormones, apoptosis in testicular cells, and sperm quality were evaluated. In females, the following was observed: alterations in estrous cycles, decreased sexual behavior, estradiol and progesterone levels, and increased uterine and vaginal epithelia. In males, we observed a decrease in sexual behavior, testosterone, and sperm quality, and apoptosis increased in testicular cells. All these effects were similar to those caused by daidzein. These results indicate that prenatal exposure to mesquite pod extract or daidzein, administered to females before and during pregnancy, can disrupt normal organizational-activational programming of reproductive physiology in female and male descendants.
... The measurement was performed using the KBr tablet method [26]. The prepared sample was ground with KBr according to a certain ratio and then compressed. ...
Genistein (Gen), a kind of natural isoflavone drug monomer with poor water solubility and low oral absorption, was incorporated into oral nanoparticles with a new mesoporous carrier material, NH2-MCM-41, which was synthesized by copolycondensation. When the ratio of Gen to NH2-MCM-41 was 1:0.5, the maximum adsorption capacity of Gen was 13.15%, the maximum drug loading was 12.65%, and the particle size of the whole core–shell structure was in the range of 370 nm–390 nm. The particles were characterized by a Malvern particle size scanning machine, XRD, Fourier transform infrared spectroscopy, scanning electron microscopy, and nitrogen adsorption and desorption. Finally, Gen-NH2-MCM-41 was encapsulated by sodium alginate (SA), and the chimerism of this material, denoted as GEN-NH2-MCM-41@SA, was investigated. In vitro release experiments showed that, after 5 h in artificial colon fluid (pH = 8.0), the cumulative release reached 99.56%. In addition, its anti-rotavirus (RV) effect showed that the maximum inhibition rate was 62.24% at a concentration of 30 μM in RV-infected Caco-2 cells, and it significantly reduced the diarrhea rate and diarrhea index in an RV-infected-neonatal mice model at a dose of 0.3 mg/g, which was better than the results of Gen. Ultimately, Gen-NH2-MCM-41@SA was successfully prepared, which solves the problems of low solubility and poor absorption and provides an experimental basis for the application of Gen in the clinical treatment of RV infection.
... Sheep exposed to chronic estrogenic pasture had permanent infertility because the cervix became defeminized and could not store spermatozoa. In ewe, genes responsible for sexual differentiation are not fully deactivated at birth; however, chronic phytoestrogen exposure leads to loss of sexual characteristics in the adult ewe [73]. ...
Phytoestrogens are nonsteroidal plant-derived compounds found in various forms in humans and animal foods. Phytoestrogens bind with mammalian estrogen receptors (ER) as they are structurally like mammalian estrogen and alter multiple mechanisms and processes, causing several disorders and diseases. Studies in humans and animals have revealed that dietary phytoestrogens play a crucial role in preventing hormone-dependent diseases and disorders such as menopausal symptoms, osteoporosis, cancer, and heart disease. Despite the potential health benefits, phytoestrogens also have several adverse effects on the reproductive health of males and females. Phytoestrogens bind with ER, interfere with the hormonal regulation of the reproductive organs, and increase the propensity of infertility, abnormal estrus cycle, and anestrous. Phytoestrogens also alter prenatal and postnatal fetal development causing various developmental abnormalities. Several studies investigated the effects of phytoestrogen compounds on reproductive health using animals, humans, and in vitro culture models. Therefore, it is important to summarize these findings for future mitigation strategies against phytoestrogens. This review focuses on the impact of specific phytoestrogens on the reproductive health of males and females and the underlying mechanisms involved in the detrimental effects of various phytoestrogen compounds. Based on the evidence obtained from the literature, we also summarized the findings in the tabular form on different reproductive tissues in males and females, including prenatal and postnatal fetal development. Phytoestrogen Phytoestrogens are a diverse class of nonsteroidal, diphenolic, estrogenic plant compounds, including prenylated flavonoids, isoflavones, coumestans, and lignans [1,2]. They are plant-derived nonsteroidal compounds structurally or functionally similar to mammalian estrogen (E 2), especially 17β-estradiol [3,4]. Phytoestrogens have an affinity for estrogen receptor-α (ER α) and-β (ER β) [3,5,6], peroxisome proliferator-activated receptor (PPAR) family [7-9] and the aryl hydrocarbon receptor (AhR) [9-11]. Phytoestrogens or their active metabolites are known to act mainly on male and female central nervous systems and reproductive systems. Phytoestrogens are poly-phenolic compounds that include over 100 molecules [12]. According to their chemical structure, they are divided into iso-flavones, flavones, coumestans, stilbenes, and lignans (Figure 1) [13]. Several plants consumed by humans and animals contain phytoestrogens [14]. Soybean products are rich in higher concentrations of isoflavones, while flaxseed is rich in lignans, clover contains coumestans [15], olives contain flavones [16], and stilbenes are found in cocoa and grape containing products, particularly red wine [15]. Mostly isoflavones from legumes, beans, and bean-containing products exhibit estrogenic activity in animals [17-21]. Second-generation soy foods are made by adding soy ingredients to a wide variety of manufactured foods. These second-generation soy foods such as tofu yogurt and soy noodle contain less isoflavone content [22-24]. Cereals, fruit, and vegetables such as flaxseed (known as linseed) contain a high concentration of lignans [19,25,26], while in whole grain cereals, vegetables, fruit, and seeds have a lesser concentration of lig-nans [17]. After consumption, phytoestrogens are metabolized by intestinal microflora, conjugated in the liver, distributed to various tissues through plasma, and excreted through urine [27].
... An interest in biological activity of isoflavones initiated when seasonal intake of Trifolium subterraneum, containing an isoflavone fraction rich in formononetin, was identified as the cause of sheep fertility problems (called "clover disease") in Western Australia around 1940 [56,57] . After thorough veterinarian investigation which followed, isoflavones were classified as phytoestrogens and occasionally even included in a category of endocrine disruptors (negative classification of environmental industrial pollutants with phenolic characteristics). ...
A survey of the current literature on natural isoflavones and their biological activity is presented. This subcategory of a large group of plant polyphenolics has particular characteristics, structural as well as pharmacological, which makes it suitable for discussion of pleiotropic activities of phytochemicals and their exploitation in healthcare, beyond the concept of selectively targeted new drugs for narrow therapeutic indication.
... Sheep exposed to chronic estrogenic pasture had permanent infertility because the cervix became defeminized and could not store spermatozoa. In ewe, genes responsible for sexual differentiation are not fully deactivated at birth; however, chronic phytoestrogen exposure leads to loss of sexual characteristics in the adult ewe [73]. ...
Phytoestrogens are nonsteroidal plant-derived compounds found in various forms in humans and animal foods. Phytoestrogens bind with mammalian estrogen receptors (ER) as they are structurally like mammalian estrogen and alter multiple mechanisms and processes, causing several disorders and diseases. Studies in humans and animals have revealed that dietary phytoestrogens play a crucial role in preventing hormone-dependent diseases and disorders such as menopausal symptoms, osteoporosis, cancer, and heart disease. Despite the potential health benefits, phytoestrogens also have several adverse effects on the reproductive health of males and females. Phytoestrogens bind with ER, interfere with the hormonal regulation of the reproductive organs, and increase the propensity of infertility, abnormal estrus cycle, and anestrous. Phytoestrogens also alter prenatal and postnatal fetal development causing various developmental abnormalities. Several studies investigated the effects of phytoestrogen compounds on reproductive health using animals, humans, and in vitro culture models. Therefore, it is important to summarize these findings for future mitigation strategies against phytoestrogens. This review focuses on the impact of specific phytoestrogens on the reproductive health of males and females and the underlying mechanisms involved in the detrimental effects of various phytoestrogen compounds. Based on the evidence obtained from the literature, we also summarized the findings in the tabular form on different reproductive tissues in males and females, including prenatal and postnatal fetal development.
... H. midae raised on formulated feeds with fishmeal and soya meal as the only protein source devoted more energy to gonad development than abalone fed diets that included only fishmeal (Wu et al. 2019). Soybean meal is rich in phytoestrogens, which are suspected to act as endocrine disruptors in H. midae (Wu et al. 2019) and other animal species (Adams 1995;Weber et al. 2001;Le Francois et al. 2010). However, Wu et al. (2019) tested soybean meal in H. midae diets and could not confirm that the flavonoids in soybean meal are responsible for the hypothesised effect on gonad development. ...
Growth rate is one of the most important factors in the farming of Haliotis midae, and somatic growth rates decline after abalone reach sexual maturity. Artificial diets are suspected to accelerate maturation, in particular when soya meal is used as a protein source, because of this plant’s high concentration of phytoestrogens. The effect of diet on the gonad development of 27-month-old farmed Haliotis midae, raised at two stocking densities, was analysed. We fed two artificial diets and a natural diet, kelp, to cultured abalone. The first artificial diet had fishmeal as its main source of protein, while in the other, Abfeed® S34, 32% of the fish meal was replaced with soya meal. For each gonad sample, the development phase was determined based on both histological criteria and the gonad bulk index (GBIn). The hypothesised link between dietary protein source and gonad development could not be established by either morphological criteria or GBIn. Similarly, stocking density did not have a significant effect on GBIn-values. GBIn values were significantly correlated to the results from the histological analyses in males and females. The results from this study suggest that artificial diets including those using soya meal are a valid alternative in the feeding of abalone. The research provides a database for future research on factors influencing gonad development in this species.
Phytoestrogens are plant-produced secondary compounds that mimic the animal sex hormone estrogen. Several legumes, including red clover, produce phytoestrogens as stress defense molecules, and climate change-driven increases in atmospheric temperature and CO2 may intensify their production. We conducted a growth chamber study to determine the effects of short-term exposure to elevated temperature (eT) and CO2 (eCO2), both alone and in combination, on phytoestrogen concentrations in red clover and cowpea. Plants were grown in ambient conditions (24/18 °C, day/night, and ~ 400 ppm CO2) and then exposed to eT (35/26 °C, day/night), eCO2 (750 ± 50 ppm), or both factors for 10 days. Phytoestrogen concentrations in cowpea vegetative tissues were below the level of detection under all conditions. In red clover, exposure to eT reduced total phytoestrogen concentration by 50%, from 3.9 to 1.9 mg/g dry matter. Most of this decrease was driven by reduced concentrations of the isoflavones formononetin and biochanin A. Elevated CO2 did not influence total phytoestrogen levels in red clover but reduced daidzein concentration by 43%. Plant physiological variables measured concurrently with phytoestrogens were weakly correlated with concentrations of individual phytoestrogen compounds and total phytoestrogens in red clover.
Objectives
The purpose of this study was to explore the molecular docking characteristics and antifertility impacts of petroleum ether extract (PEEPO) and chloroform (CHEPO) derived from Pandanus odoratissimus (PO) leaves.
Methods
TriposSybyl-X 2.1 for molecular docking and Swiss ADME for ADME predictions were used. Antifertility activity was determined by using two in vivo animal models, with a focus on estrogenic/antiestrogenic activity and anti-implantation effects.
Results
The findings showed that at different doses (100, 200, and 400 mg/kg), PEEPO had more anti-implantation effect than CHEPO. After taking either extract orally for up to 4,000 mg/kg, no acute toxicity was found. Furthermore, both extracts substantially raised blood oestrogen levels while lowering serum cholesterol and LDL levels, improving their antiimplantation and estrogenic activities, whether given alone or in combination with ethinyl estradiol. Molecular docking scores suggested strong interactions between phytochemicals in the extracts and estrogen receptors. ADME studies highlighted four phytochemicals present in PO leaves, showing high gastrointestinal absorption, blood-brain barrier permeability, and negative Log Kp values, indicating their potential as antifertility agents.
Conclusions
The phytochemicals in both PEEPO and CHEPO demonstrated promising antifertility potential and interactions with estrogen receptors. Isolation of these phytochemicals could lead to the development of effective herbal antifertility formulations.
In recent years, there has been a trend towards hyperoestrogenic feeding methods in
field conditions, particularly in dairy small ruminants. This study aimed to investigate
the effect of alfalfa supplemented ration in the prepartum period on the occurrence
of udder oedema in dairy ewes and its impact on fertility problems (dystocia, vaginal
prolapse, uterine prolapse, retained placenta) and diseases (mastitis, udder dermatitis)
occurring in the postpartum period. In addition, it aimed to follow up the data
on maternal rejection behaviours and litter viability, which are believed to affect the
future productivity and fertility of the herd. The ewes were divided into two groups:
the oedema group (n = 20) and the control group (n = 23). For trial purposes in the
oedema group, primiparous animals were provided with alfalfa supplementation. The
control group consisted of ewes fed the same ration but without alfalfa supplementation.
Ingredient analysis of the rations was performed in the groups. In biochemical
analyses, the oedema group demonstrated significantly higher levels of serum urea
(p < .05), Ca (p < .000) and Ca/P ratio (p < .01) compared to the control group. Clinical
mastitis (0–7 days, p = .051) and (8–30 days, p = .149) were reported at a higher rate
in the oedema group compared to the control group. Udder dermatitis cases were
more common in the oedema group (p = .005). The mother's rejection of the lamb was
higher in the oedema group. Dystocia was determined to be 30% in the oedema group
(p = .023). In conclusion, applying hyperoestrogenic feeding strategies during the periparturient
period firstly exacerbates physiological udder oedema in ewes, thus predisposing
them to various herd fertility problems. This feeding strategy, frequently
encountered in field conditions, seriously harms the physiological fertility process.
Animal nutritionists have incessantly worked towards providing livestock with high-quality plant protein feed resources. Soybean meal (SBM) has been an essential and predominantly adopted vegetable protein source in livestock feeding for a long time; however, several SBM antinutrients could potentially impair the animal's performance and growth, limiting its use. Several processing methods have been employed to remove SBM antinutrients, including fermentation with fungal or bacterial microorganisms. According to the literature, fermentation, a traditional food processing method, could improve SBM's nutritional and functional properties, making it more suitable and beneficial to livestock. The current interest in health-promoting functional feed, which can enhance the growth of animals, improve their immune system, and promote physiological benefits more than conventional feed, coupled with the ban on the use of antimicrobial growth promoters, has caused a renewed interest in the use of fermented SBM (FSBM) in livestock diets. This review details the mechanism of SBM fermentation and its impacts on animal health and discusses the recent trend in the application and emerging advantages to livestock while shedding light on the research gap that needs to be critically addressed in future studies. FSBM appears to be a multifunctional high-quality plant protein source for animals. Besides removing soybean antinutrients, beneficial bioactive peptides and digestive enzymes are produced during fermentation, providing probiotics, antioxidants, and immunomodulatory effects. Critical aspects regarding FSBM feeding to animals remain uncharted, such as the duration of fermentation, the influence of feeding on digestive tissue development, choice of microbial strain, and possible environmental impact.
Phoma black stem and leaf spot disease ( Phoma medicaginis ) not only destroys annual Medicago spp. forage and seed yield but also reduces herbage quality by consequent phytoestrogen production that reduces ovulation of grazing animals. Two controlled environment studies evaluated the effects of plant developmental stage in annual Medicago rugosa ‘Paraponto’ and M . scutellata ‘Sava’ and different inoculum concentrations of P . medicaginis in M . littoralis ‘Harbinger’ and M . polymorpha ‘Serena’ on disease development and coumestrol production. Disease incidence and severity and coumestrol production were dependent on plant developmental stage, cultivar and inoculum level (all p ≤ 0.001). Disease was least in 4‐week‐old plants; highest coumestrol was in inoculated 10‐week‐old Sava (1353 mg/kg) and least coumestrol in uninoculated 4‐week‐old Paraponto (87 mg/kg); and there was a positive correlation of disease incidence/severity factors with coumestrol across cultivars and plant growth stages ( p < 0.001). Disease levels and coumestrol production were determined by inoculum concentration and cultivar (both p ≤ 0.001). Highest coumestrol was in Serena inoculated with 10 ⁷ conidia/mL (265 mg/kg); lowest coumestrol was in uninoculated Harbinger (6 mg/kg); and there was a significant positive correlation of disease incidence/severity factors with coumestrol across cultivars and inoculum concentrations ( p < 0.001). These studies emphasize both the opportunity for farmers to better use annual Medicago spp. stands for grazing reproducing animals early in the growing season when both disease and coumestrol levels are lowest, and the need for heightened farmer vigilance at later growth stages with greater disease and consequent phytoestrogen risk for grazing animals.
Over the last decades, global concerns regarding possible adverse health effects of chemical pollutants on the hormonal systems of living organisms in wildlife and humans are constantly growing. Endocrine-active and endocrine-disrupting chemicals (EDC) belong to a heterogeneous class of exogenous chemicals, including various persistent anthropogenic contaminants, pesticides, distinct substances used in consumer products, and also natural compounds. Exposure through the food chain is considered essential for most EDC, while they may enter the food chain as residues from animal- or plant-based food production (e.g. pesticides or pharmaceutical residues), may be released from food contact materials, may be present due to natural contamination (e.g. mycoestrogens), may enter via a polluted environment and also as natural plant food ingredients (e.g. phytoestrogens). The complexity of the subject is due to: a) the ubiquitous occurrence and hardly possible avoidance of many substances with supposed endocrine properties, b) the scientific disagreement among experts and the huge number of partly controversial study outcomes and c) the increasing pressure of the public, necessitating a higher level of transparency and clear-cut orientation with respect to avoidance and reduction strategies.In this light, the current review intends to provide an overview of the historical and regulatory developments regarding the topic of EDC, discusses the important difference between endocrine-active and disruptive substances and presents some key characteristics of endocrine acting substances for a better understanding of their relevance for the food chain including possible long-term effects, windows of sensitivity, low-dose and possible “cocktail” effects. In addition, a comprehensive overview on the different exposure paths of endocrine-active and disruptive substances in the food chain is given, with both a focus on naturally occurring food ingredients and possible contaminations from external sources.
Isoflavones represent a class of phytoestrogens present in plants. In dairy cows, dietary isoflavones have been shown to negatively affect reproductive performance. To the best of our knowledge, no studies have yet been conducted to determine if calves are pre- or neonatally confronted with isoflavones and their metabolites. In the present study, we hypothesize that isoflavones are passed on from the dam to the offspring in utero. Twenty-three pregnant Holstein Friesian dams and their calves, originating from three commercial dairy farms in Belgium, were included. Heparin blood samples were collected during the first, second, and third trimester of gestation from all pregnant dams. Heparin blood and hair samples were obtained from the offspring within 24 h after parturition. Colostrum samples were collected from a subset of eight dams to determine the concentration of isoflavones and their metabolites. During the first and second trimester of gestation, the dams were fed either a youngstock (nulliparous dams) or a lactation (multiparous dams) diet. During the third trimester, both groups received a similar dry cow diet. Genistein and daidzein levels were unaffected by diet type, while their metabolite [equol, dihydrodaidzein (DHD), and o-desmethylangolensin (ODMA)] concentrations were significantly higher in the lactation group. Furthermore, metabolite concentrations decreased significantly during gestation. Isoflavones and their metabolites were detected in all colostrum samples. No correlation could be found between levels in colostrum and blood of pregnant dams or calves. Peripheral levels of isoflavones and their metabolites were significantly lower in newborn calves in comparison to their dams. Genistein and daidzein concentrations were found to be significantly higher in the calves' hair versus blood samples, suggesting prenatal exposure to isoflavones for an extended period of time. In contrast, no isoflavone metabolites were detected in the calves' hair samples. This is the first study to demonstrate that dairy calves are exposed to isoflavones during the developmentally most sensitive period of their lives. Results obtained pave the way for more extensive research to examine which effects isoflavones might have on developing organ systems like the reproductive system.
1. Giriş 1962 yılında basılan Sessiz Bahar kitabında Rachel Carson, kontrolsüz kimyasal kullanımının hava, toprak, yeryüzü ve yüzey suyu kirliliğine neden olarak hayvanların ölümüne ve olası insan sağlığı sorunlarına yol açabileceğini anlatmıştı. Aynı kitabında ekosistemin yüz binlerce yeni kimyasal bileşikle geri dönüşü olmayan bir şekilde zarar gördüğünden de bahsetmişti [1]. Buna ek olarak bu yüzyılın başında hayvan sahipleri sığırlarının üreme sistemlerinde kusurlar keşfettiler. Daha sonra bu bozuklukların, kumestrol adı verilen östrojenik maddeden kaynaklandığı anlaşıldı [2]. 1992'de Colborn ve ark. [3] , bilimsel literatürde endokrin aracılı toksisitenin potansiyel etkileri hakkında bir hipotez üretti. ABD Çevre Koruma Ajansı (EPA), 1990'ların ortasında ilk uluslararası kongreyi düzenledi, bu kongrenin ana konuları östrojenik pestisitlerin olası etkileri ve sağlık etkileri idi. Bilimsel kanıtlar, organoklorinler [poliklorlu bifeniller (PKB'ler), diklorodifenildikloroetilen (DDE)] tarafından kirletilen okyanuslarda bulunan balina ve yunuslardaki olumsuz sonuçlar dahil olmak üzere, endokrin bozucuların hayvan habitatı üzerindeki etkilerini özetlemektedir [4]. Dietilstilbestrol (DES)'ün insan sağlığı üzerine etkileri, düşük yapmayı önlemek için ilacın geçmişte kullanılması nedeniyle iyi bilinmektedir. DES'e doğum öncesi maruziyet, vajina ve servikste berrak hücreli adenokarsinom, genital sistemde anormallik ve erkek çocuklarının üreme yolu sekelleri, kız genital organlarının sekellerine neden olmuştur [5]. Endokrin Bozucu Kimyasallar (EBK), plastik kavanozlar, oyuncaklar, kozmetikler, teneke kutular, deterjanlar, alev geciktiriciler, gıda koruyucuları ve böcek öldürücüler dahil olmak üzere çok çeşitli günlük tüketim ürününde mevcuttur. EBK'ler memelilerin endokrin sistemine müdahale eder. EBK'ların varlığı, sağlık için ciddi sonuçlara yol açabilen endokrin hormon aktivitesini inhibe edebilir veya taklit edebilir [6] .
1. Giriş 1962 yılında basılan Sessiz Bahar kitabında Rachel Carson, kontrolsüz kimyasal kullanımının hava, toprak, yeryüzü ve yüzey suyu kirliliğine neden olarak hayvanların ölümüne ve olası insan sağlığı sorunlarına yol açabileceğini anlatmıştı. Aynı kitabında ekosistemin yüz binlerce yeni kimyasal bileşikle geri dönüşü olmayan bir şekilde zarar gördüğünden de bahsetmişti [1]. Buna ek olarak bu yüzyılın başında hayvan sahipleri sığırlarının üreme sistemlerinde kusurlar keşfettiler. Daha sonra bu bozuklukların, kumestrol adı verilen östrojenik maddeden kaynaklandığı anlaşıldı [2]. 1992'de Colborn ve ark. [3] , bilimsel literatürde endokrin aracılı toksisitenin potansiyel etkileri hakkında bir hipotez üretti. ABD Çevre Koruma Ajansı (EPA), 1990'ların ortasında ilk uluslararası kongreyi düzenledi, bu kongrenin ana konuları östrojenik pestisitlerin olası etkileri ve sağlık etkileri idi. Bilimsel kanıtlar, organoklorinler [poliklorlu bifeniller (PKB'ler), diklorodifenildikloroetilen (DDE)] tarafından kirletilen okyanuslarda bulunan balina ve yunuslardaki olumsuz sonuçlar dahil olmak üzere, endokrin bozucuların hayvan habitatı üzerindeki etkilerini özetlemektedir [4]. Dietilstilbestrol (DES)'ün insan sağlığı üzerine etkileri, düşük yapmayı önlemek için ilacın geçmişte kullanılması nedeniyle iyi bilinmektedir. DES'e doğum öncesi maruziyet, vajina ve servikste berrak hücreli adenokarsinom, genital sistemde anormallik ve erkek çocuklarının üreme yolu sekelleri, kız genital organlarının sekellerine neden olmuştur [5]. Endokrin Bozucu Kimyasallar (EBK), plastik kavanozlar, oyuncaklar, kozmetikler, teneke kutular, deterjanlar, alev geciktiriciler, gıda koruyucuları ve böcek öldürücüler dahil olmak üzere çok çeşitli günlük tüketim ürününde mevcuttur. EBK'ler memelilerin endokrin sistemine müdahale eder. EBK'ların varlığı, sağlık için ciddi sonuçlara yol açabilen endokrin hormon aktivitesini inhibe edebilir veya taklit edebilir [6] .
During early embryonic development, late fetal growth, puberty, adult reproductive years, and advanced aging, bovine and human ovaries closely share molecular pathways and hormonal signaling mechanisms. Other similarities between these species include the size of ovaries, length of gestation, ovarian follicular and luteal dynamics, and pathophysiology of ovarian diseases. As an economically important agriculture species, cattle are a foundational species in fertility research with decades of groundwork using physiologic, genetic, and therapeutic experimental techniques. Many technologies used in modern reproductive medicine, such as ovulation induction using hormonal therapy, were first used in cows before human trials. Human ovarian diseases with naturally occurring bovine correlates include premature ovary insufficiency (POI), polycystic ovarian syndrome (PCOS), and sex-cord stromal tumors (SCSTs). This article presents an overview of bovine ovary research related to causes of infertility, ovarian diseases, diagnostics, and therapeutics, emphasizing where the bovine model can offer advantages over other lab animals for translational applications.
It well documented that isoflavones have tremendous effects on human and animal health and on some plant species especially legumes. In this chapter, we summarized their positive and negative effects on human health including the prevention of cancer, cardiovascular diseases, osteoporosis, menopausal symptoms in women, effects on menstrual cycles, thyroid function, memory and learning ability, brain development, Alzheimer’s disease, obesity reduction, reproduction, bone density, diabetes, immunity, and other effects. In animals, we discussed the effects of isoflavones on the prevention of certain types of cancer, cardiovascular diseases, thyroid gland function, obesity reduction, reproduction, diabetes, immunity, and other effects. Positive effects of isoflavones on legume plants have been also discussed.
Change in genetic composition of a mixed population of subterranean clover was studied at Kalangadoo in the south-east of South Australia. The seeds from an experiment in which 25 late-maturing strains were compared, were sampled in January 1977, 19 years after the plants were originally sown in 1958. Quadrats along three transects over the approximate position of the old plots were sampled and seed yields measured. The soil was analysed for several chemical and physical properties at the site of each quadrat. Thirty seeds from each sample were germinated in a glasshouse and the resulting seedlings planted out as spaced plants. These were identified on the basis of flowering time and morphological variables; in this way the seed pool of each strain at each quadrat site was determined. Seed pools were adjusted for variation in distance of original plots from the transects by estimating the real position of each plot relative to the transect and calculating the relationship between seed yield and estimated distance. Highest adjusted seed pools were produced by CPI 14454B (820 kg ha-1), CPI 12695 (626 kg ha-1), Eden Valley (502 kg ha-1), and CPI 14197A (476 kg ha-1). Cultivars Mt Barker and Tallarook were also common, but it was deduced from their distribution that they had been continuously introduced to the site from surrounding fields by livestock. All but six of the original strains were recovered in the sampling. Also present were many divergent strains, which yielded 228 kg ha-1 or 31 % of the average seed yield of 744 kg ha-1. Twenty-four of the original 25 strains and five others-Woogenellup, Yarloop, Trikkala, Clare and a divergent strain naturalized at Kalangadoo-were sown in small plots. Twenty-five agronomic variables were measured, including seasonal herbage yields, petiole lengths, leaf areas, isoflavone contents, phosphorus and sulfur uptakes, above- and below-ground seed yields, seed and seedling sizes and permeability of seed coats. The fourth component of a principal component analysis of the data was related to seed pool (P < 0.001), and it is suggested that the variables contributing to this component are important in predicting the success of a strain at Kalangadoo. The most successful tended to have high yields of buried seed, high yields of herbage and long petioles in winter, high formononetin content, early maturity and small seedlings. The results are discussed in terms of factors affecting success, generation of new genetic diversity, and field implications.
Prolonged exposure to oestrogen causes transsexual redifferentiation in the ewe, which can be assessed experimentally by measuring the cross-sectional area of lamina propria (lp) tissue lying underneath the cervical folds in the mid-cervix. The extent of transsexual redifferentiation caused by prolonged exposure to clover oestrogens was measured in ewes from 13 farms in Western Australia. Groups of 90-157 mature ewes were mated under normal farming husbandry, and consigned to the abattoirs 6-8 weeks later. Histological sections were prepared from the mid cervix of 37-80 ewes from each flock. The area of lp was increased in ewes from the three farms with a history of infertility due to oestrogenic clover, when compared with ewes from the four farms in non-clover areas. Overall, the mean area of lp in ewes from the 13 farms was correlated (r = 0.81, P < 0.01) with the proportion of non-pregnant ewes, but less so with the potential lambing rate as judged by the number of foetuses/100 ewes (r = -0.51, N.S.). This contrast came about because flocks affected by oestrogen-induced transdifferentiation also tended to have higher ovulation rates; a regression including both the ovulation rate and area of lp accounted for 89010 of the variation between flocks in potential lambing rate. It is concluded that clover oestrogens are an important cause of the relatively high proportion of ewes which fail to lamb in Western Australia.
Three years' results of sheep uterine weight bioassays on a range of clover swards are presented. Trifolium pratense L. (var. Grasslands Hamua Broad) and Trifolium subterraneum L. (var. Dinninup, Dwalganup, Tallarook, and Yarloop) showed high activity whenever they were green. Trifolium fragiferum L. (mixed+Palestine), Trifolium repens L. (var. Victorian Irrigation), and Trifolium subterraneum L. (var. Bacchus Marsh, Howard, Marrar, and a breeder's selection) showed variable activity; Medicago sativa L. (var. Hunter River), Medicago littoralis (Rhode), Trifolium alexandrinum L., Trifolium incarnatum L. (var. Dixie), and Trifolium repens L. (var. Grasslands Huia and Ladino) have not shown activity. Spraying two of the clovers with paraquat and dosing the sheep with cobalt sulphate had no effect on activity. There was a strong seasonal trend with highest activity in midwinter and lowest in mid spring. The relationships between chemical assay and bioassay results are discussed. There is reasonable evidence that the activity of Victorian Irrigation white clover is not related to any of the compounds being measured.
Epidemiologic studies revealed low mortality in hormone-dependent cancer in Japanese women and men consuming a traditional diet. We previously found that certain diphenolic food components, lignans and isoflavonoids, which are converted to biologically active hormone-like substances by intestinal microflora, may be cancer-protective agents. Therefore, we studied urinary excretion of these compounds (enterolactone, enterodiol, daidzein, equol, and O-desmethylangolensin) in 10 women and 9 men in a rural village south of Kyoto, Japan. The subjects consumed a typical low-fat diet with much rice and soy products, fish, and vegetables. An isotope-dilution gas chromatographic-mass spectrometric method was used for the assays. The urinary excretion of lignans was low but that of the isoflavonoids was very high. The excretion of isoflavonoids correlated with soybean-product intake. The low mortality in breast and prostate cancer of Japanese women and men, respectively, may be due to the high intake of soybean products.
Coumestrol, a phytoestrogen, was determined in animal feeds by high-performance liquid chromatography. The coumestrol concentration was determined in feeds being fed to animals showing physiological effects of high estrogen levels and to animals where no physiological effect was noticed. The data implies that animals fed haylage containing 37 ppm coumestrol or more as their major feed will show physiological estrogenic effects.
Epidemiologic studies revealed low mortality in hormone-dependent cancer in Japanese women and men consuming a traditional diet. We previously found that certain diphenolic food components, lignans and isoflavonoids, which are converted to biologically active hormone-like substances by intestinal microflora, may be cancer-protective agents. Therefore, we studied urinary excretion of these compounds (enterolactone, enterodiol, daidzein, equol, and O-desmethylangolensin) in 10 women and 9 men in a rural village south of Kyoto, Japan. The subjects consumed a typical low-fat diet with much rice and soy products, fish, and vegetables. An isotope-dilution gas chromatographic-mass spectrometric method was used for the assays. The urinary excretion of lignans was low but that of the isoflavonoids was very high. The excretion of isoflavonoids correlated with soybean-product intake. The low mortality in breast and prostate cancer of Japanese women and men, respectively, may be due to the high intake of soybean products.
Four trials with a total of 1750 Perendale ewes were conducted to determine the effect of feeding lucerne on ovulation rate and lambing performance. Levels of up to 600 ppm coumestans in lucerne leaf, associated with fungal infection, depressed ovnlation rate and lambing by 34% and 14.6% respectively. In the absence of fungal infestation no coumestans were found and stage of regrowth had 110 effect on lambing performance. A negative linear relationship between coumestan ccntent of the diet (x) and ovulation rate (y) was determined (y = 1.382 - O.004x). Levels of coumestans as low as 25 ppm in the diet depressed the ovulation rate of ewes fed lucerne pellets for 35 days. The depression in ovulation rate of ewes fed a high (100 ppm) level of coumestans was overcome by treatment with pregnant mare's serum gonadotrophin. It is suggested that coumestans exert their effect by interference with the release of follicle stimulating hormone from the pituitary gland.
Studies were conducted on changes in coumestrol content of alfalfa which occurred in each of two germ‐plasm pools as a result of recurrent selection practiced previously for resistance to two foliar diseases, common leafspot ( Pseudopeziza medicaginis (Lib.) Sacc.) and rust ( Uromyces striatus Schroet. var. medicaginis (Pass.) Arth.). For each disease, plants of each selection cycle were established from remnant seed and inoculated under uniform, controlled conditions. Selection for increased resistance to common leafspot resulted in fewer leafspots and lower coumestrol content in plants of both pools. Coumestrol content was positively associated with lesion size and number. In the rust phase of the study, coumestrol content was also positively associated with lesion size and number except in the most susceptible class. Urediospores were high in coumestrol, a factor which suggested that the massive spore fall which occurred in very susceptible plants resulted in a loss of coumestrol in very susceptible individuals. Selection in alfalfa for resistance to common leafspot and rust can be expected to reduce the increase in coumestrol content which results from growing the crop under conditions favorable for development of these diseases.
A method is presented for the specific determination in plasma or adipose tissue of sheep of the phyto-oestrogens genistein (G), biochanin A (BA), formononetin (F), daidzein (D), pratensein, and coumestrol. The method is based on selective extraction, paper chromatography, spectrophotometry and fluorometry, and use of radioactive recovery standards. A modification including gas chromatography is also described. Intraruminal administration to sheep of the synthetic isoflavones G, BA, or F gave rise within 2½ hr to detectable blood levels of the compound infused. In addition, intraruminal administration of BA and F was followed by the appearance of G and D, respectively, in blood and fat depots. Such O-demethylation at the C4 position was also observed after intramuscular injection of BA or F, and in sheep grazing subterranean clover (Trifolium subterraneum L.) and red clover (T. pratense). Plasma levels of free G above 5 µg/100 ml (excluding circulating isoflavone conjugated as glucuronide) were associated with maximal uterine growth response in ovariectomized ewes, while levels of 1–5 µg/100 ml appeared to elicit a graded uterine response; free plasma F and D levels above 0.5 ¦g/100 ml seem to be required for detectable uterotrophic action in the 5-day assay used. G, BA, F, and D were present in the plasma of sheep grazing subterranean clover var. Yarloop in concentrations adequate to explain the observed uterine growth response, but in sheep grazing red clover, the plasma levels seemed too low to account fully for the oestrogenic action of this pasture. No free isoflavones were detected in plasma from sheep grazing subterranean clover var. Marrar, despite the high isoflavone content of the pasture.
Sixteen ewes were drawn from each of two ewe flocks, one of which had grazed on oestrogenic pastures for annual periods over the previous 5 years ("clover" treatment) while the other grazed on green oats ("oats" treatment). Fertility of ewes on the clover treatment had decreased progressively, whereas in those on the oats treatment it had remained high. Oestrous ewes were allocated alternately to receive either two or eight services then killed 24 hr post coitus and the numbers of sperm in the cervix, uterus, and fallopian tubes determined. There was no difference in ovarian activity between the two groups; however, highly significant differences were found in the numbers of sperm recovered from the cervix, uterus, and fallopian tubes. Average sperm numbers per fallopian tube were 17,160 and 350 for ewes on the oats and clover treatments respectively. In addition to the reduction in sperm numbers, both the percentage of motile sperm flushed from the cervix and the proportion of recovered ova with sperm attached to the zona pellucida were lower in ewes on the clover treatment. The results suggest that primary failure of sperm transport in ewes on the clover treatment occurred when sperm did not enter the cervix in adequate numbers following service. The significance of these observations in relation to possible causal mechanisms is discussed.
This study examined the effects of diet on the development of prostatitis in male rats. Adult male rats were placed on either of two specially formulated diets which differed from one another by the presence or absence of soy as the protein source. A third group of rats (control) was fed standard laboratory rat chow which also includes soy as a source of protein. After 11 weeks, it was found that rats maintained on soy-free diet developed prostatitis mainly in the lateral lobe of the prostate. Increased severity and incidence of prostatitis in rats maintained on the soy-free diet coincided with a significant decrease in urinary excretion of various phytoestrogens. There was no evidence of prostatitis in rats maintained on soy-containing diets. Urinary excretion of phytoestrogens in rats maintained on soy-containing diet was also not different from controls. These results suggest that soy as a dietary source plays a protective role against the development of prostatitis in rats, and indicate that the ventral, lateral and dorsal lobes of the rat prostate have different sensitivities to alterations in dietary factors.
In Australia, more than 1 million ewes have permanently damaged reproductive tracts because they have been grazed on oestrogenic pasture. These effects occur in the absence of classical clinical "clover disease". The lesions result from an "organisational" action of oestrogen, causing a mild sexual transdifferentiation to occur in ewes during adult life, with the main lesion being found in the cervix. Diagnosis of the problem depends primarily on detection of the pathological changes, rather than history or clinical signs. On average, affected flocks have around a 10% increase in non-pregnant ewes, but most farmers can achieve an acceptable lambing rate by increasing their management and feed inputs to produce more twin lambs. Agronomic approaches have been used in the past to combat "clover disease", but further progress with the present problem may depend on the development of animal-based solutions.
Interaction in the immature mouse of potent oestrogens with the weak utero-vaginotrophic (UV) compounds, coumestrol, genistein, dimethyl-stilboestrol, norethisterone acetate and megestrol acetate though sometimes additive at very low doses appeared to be essentially antagonistic at higher doses.
In particular, the weak oestrogens coumestrol and genistein, found in certain plants, markedly inhibited the UV action of potent oestrogens, e.g. oestradiol-17β, oestrone and diethylstilboestrol and this effect may account in part for the anti-oestrogenic activity of extracts of these plants.
Some differences in the ability of different oestrogens to promote uterine growth relative to vaginal growth were observed.
During the stall feeding period 1982-1983, it was established that serious fertility disturbances, indicating oestrogenic stimulation, had occurred in a herd of cattle in an area supported by the College of Veterinary Medicine's ambulatory clinic. Whilst investigating the cause of these disturbances it was proven that the silage administered during this period was prepared almost entirely from pure red clover aftergrowth. The oestrogenic isoflavone content of the silage (liquid chromatograph examination) and the oestrogenic strength (bioassay) were considerably great. When feeding with the fodder was subsequently discontinued the disturbances ceased to occur and the cows became pregnant more easily. On the basis of the aforementioned incidences it was ascertained that plant oestrogens were almost certainly the cause of the fertility disturbances.
Phytoestrogens Cheeke ( E d . ) Toxicants of Plant Origin. Vol I V . Phenolics. p 23
- N R Adams
Adams, N. R. 1989. Phytoestrogens. In: P. R. Cheeke ( E d. ) Toxicants of Plant Origin. Vol I V. Phenolics. p 23. CRC Press, Boca
Raton, FL.
Phytoestrogen activity of two species of native B.C. legumes
- J S Gammie
- W D Kitts
Gammie, J. S., and W. D. Kitts. 1972. Phytoestrogen activity of two
species of native B.C. legumes. J. Anim. Sci. 34:914 (Abstr.).