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Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate
Abstract
To evaluate the possible biochemical effect of diet and heredity on the rates of monozygotic and dizygotic twinning.
In that insulin-like growth factor (IGF) has been found to be elevated in cows selected for their demonstrated increased twinning rate, the effect of agents that influence the level of IGF in women was examined. This was correlated with their prior history of singleton versus twin birthing. In particular, the effect of diets consisting of or excluding animal products that have elevated IGF content (e.g., milk) was considered.
Vegan women, who exclude dairy products from their diets, have a twinning rate which is one-fifth that of vegetarians and omnivores.
The results reported here support the proposed IGF model of dizygotic twinning. Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation.
... IGF is a protein component of milk; bovine milk has a lower level of IGF than human milk, in general [5]. Recent reports support the view that twinning in humans is also related in some way with IGF [6][7][8]. Somatotropinstimulated IGF augmentation often induces ovarian hyperstimulation in subfertile women undergoing in vitro fertilization [9]. On the other hand, one small study found no significant difference in plasma follicle stimulating hormone (FSH) between mothers of Dizygotic (DZ) twins and mothers of singletons at any stage of the menstrual Several reported observations relating lactation, IGF, and twinning are pertinent to this issue. ...
... Data relating total months of lactation in prior pregnancies and the number of babies in the most recent spontaneous gestation (singleton or multiple) were sought. Respondents who had participated in prior studies in this series [6][7][8] were also asked by e-mail to provide information here. It was emphasized to all potential participants that results would be treated anonymously and confidentially. ...
... Serum levels of IGF are proportionate to the intake of milk [40]. Voluntary vegans, who consume no animal products, have lower serum IGF and a lower rate of twinning than omnivores [7]. Thus, when combined with the data reported here, it could be concluded that the chance of twinning in humans is correlated with the extent of prior lifetime experience lactating and consuming milk. ...
Citation:
Steinman G. Mechanisms of Twinning IX: Influence of Prior Lactation.
Ann Nutr Disord & Ther
. 2017;
4(3): 1047.
Ann Nutr Disord & Ther - Volume 4 Issue 3 - 2017
ISSN : 2381-8891
| www.austinpublishinggroup.com
Steinman. © All rights are reserved
Annals of Nutritional Disorders & Therapy
Open Access
Abstract
Background:
Prior studies have emphasized the apparent role of insulin-
like growth factor in promoting twinning. In light of the known elevation of this
growth factor during bovine lactation, a study was now designed to evaluate the
possible role of this biochemical phenomenon in human double ovulation.
Research Aim:
To examine the relationship of human spontaneous twinning
with a history of prior lactation.
Methods:
Through published announcements and randomly distributed
questionnaires, volunteers were sought who had previously delivered viable
gestations at least twice. Mothers of spontaneously conceived singletons, twins,
and/or triplets who had delivered viable gestations in at least two separate
pregnancies were included. These women were asked to supply anonymously
retrospective information about their breast-feeding history in pregnancies. Data
from the most recent gestations were separated by final delivery size (singletons
versus multiples). The total duration of breast-feeding in prior pregnancies was
noted and segregated by whether the nursing had been exclusive or combined
with cow’s milk or formula by bottle. Statistical significance of prior breastfeeding
versus bottle/feeding was confirmed.
Results:
On average, women delivering twins or triplets had exclusively
breast-fed more often (71.4%
vs
. 17.2%) and longer (21.4
vs
. 8.6 months) in
total in their previous pregnancies than those giving birth to singletons (p<.001).
Furthermore, mothers who themselves had been breastfed as neonates were
more likely to conceive multiples as adults.
Conclusion:
The chance of twinning in later gestations appears to correlate
with the total duration many women lactated in earlier pregnancies. The longer
and the more exclusively these gravid as had breast-fed previous neonates, the
greater was their likelihood of twinning in their most recent pregnancy. Having
been nursed as a neonate also seems to be associated with conceiving twins
... In a just-released study of 1042 women, Steinman (2006b;Bakalar, 2006) found that eating dairy products increased the chances of women having fraternal twins by a factor of five. This result was based on a comparison of birth outcomes between women who occurring situation in which to test related hypotheses. ...
... However, Rasak Tijani, medical director of the Olugbon Hospital, favors a genetic explanation, claiming that residents of other areas follow the same diet and culture, yet do not show the same elevated twinning rate (Ibagere, 2002). A computer search did not turn up current research, and the study linking yams and twinning cited by Steinman (2006b) was published in 1986. More timely research on this question would help resolve this issue. ...
... It was suggested that greater abundance and stability of food sources on the archipelego may be an explanation. Steinman's (2006b) paper presents provocative work that deserves followup. It would be important to know, for example, if the women consuming twins in two other sets have joined: Ronde and Tiki Barber, and Kato and Wasswa Serwanga http://www.twinstuff.com/twinsnfl.htm). ...
The nature and frequency of quadruplet births are reviewed, followed by a close-up look at the 6-year-old monozygotic Mathias quadruplets. This essay is followed by reviews of new twin research on color–number association, male–female twins' finger-length ratios, and links between twinning and dietary practices. The article finishes by focusing on unusual twin athletes in football, basketball and golf, and on twin co-authors of a new book on the 1972 silver medal victory by the United States hockey team.
... In a just-released study of 1042 women, Steinman (2006b;Bakalar, 2006) found that eating dairy products increased the chances of women having fraternal twins by a factor of five. This result was based on a comparison of birth outcomes between women who occurring situation in which to test related hypotheses. ...
... However, Rasak Tijani, medical director of the Olugbon Hospital, favors a genetic explanation, claiming that residents of other areas follow the same diet and culture, yet do not show the same elevated twinning rate (Ibagere, 2002). A computer search did not turn up current research, and the study linking yams and twinning cited by Steinman (2006b) was published in 1986. More timely research on this question would help resolve this issue. ...
... It was suggested that greater abundance and stability of food sources on the archipelego may be an explanation. Steinman's (2006b) paper presents provocative work that deserves followup. It would be important to know, for example, if the women consuming twins in two other sets have joined: Ronde and Tiki Barber, and Kato and Wasswa Serwanga http://www.twinstuff.com/twinsnfl.htm). ...
The nature and frequency of quadruplet births are reviewed, followed by a close-up look at the 6-year-old monozygotic Mathias quadruplets. This essay is followed by reviews of new twin research on color-number association, male-female twins' finger-length ratios, and links between twinning and dietary practices. The article finishes by focusing on unusual twin athletes in football, basketball and golf, and on twin co-authors of a new book on the 1972 silver medal victory by the United States hockey team.
... 3 The author conducted thirty-eight semi-structured interviews with active and retired scientists, civil servants, industry representatives, politicians and interest group actors. 4 Two particularly high profile studies have associated IGF-1 with a higher risk of diabetes (Baur et al, 2006) and identified milk produced by rbST administered cows as one of three major contributors to increased human twinning (Steinman, 2006). ...
... The author conducted thirty-eight semi-structured interviews with active and retired scientists, civil servants, industry representatives, politicians and interest group actors. 4 Two particularly high profile studies have associated IGF-1 with a higher risk of diabetes(Baur et al, 2006) and identified milk produced by rbST administered cows as one of three major contributors to increased human twinning(Steinman, 2006). ...
Almost two decades ago, Peter M. Haas formulated the epistemic community framework as a method for investigating the influence of knowledge-based experts in international policy transfer. Specifically, the approach was designed to address decision-making instances characterized by technical complexity and uncertainty. Control over the production of knowledge and information enables epistemic communities to articulate cause and effect relationships and so frame issues for collective debate and export their policy projects globally. Remarkably, however, we still know very little about the variety of ways in which decision-makers actually learn from epistemic communities. This article argues that variety is best captured by differentiating the control enjoyed by decision-makers and epistemic communities over the production of substantive knowledge (or means) that informs policy from the policy objectives (or ends) to which that knowledge is directed. The implications of this distinction for the types of epistemic community decision-maker learning exchanges that prevail are elaborated using a typology of adult learning from the education literature which delineates four possible learning situations. This typology is then applied to a comparative study of US and EU decision-makers' interaction with the epistemic community that formed around the regulation of the biotech milk yield enhancer bovine somatotrophin (rbST) to illustrate how the learning types identified in the model play out in practice.
... Our finding of a 1.7% prevalence rate is slightly higher than global averages, aligning with previous research suggesting regional variations in twinning rates [5]. The urban-rural divide, with urban areas showing a marginally higher prevalence, possibly points towards the influence of factors such as increased access [6]. However, this difference was not statistically significant and warrants further investigation. ...
Background: Dizygotic twin pregnancies present unique challenges and implications for maternal and neonatal health. In Bangladesh, with its rapidly changing socioeconomic landscape and rich cultural traditions, there is a need to explore the prevalence and outcomes of such pregnancies. Objective: This study aimed to determine the prevalence of dizygotic twin pregnancies in Bangladesh, evaluate associated maternal and neonatal health outcomes, and understand the influence of socio-cultural, economic, and healthcare-related factors. Methods: A cross-sectional study involving 384 participants with dizygotic twin pregnancies was conducted across urban and rural regions of Bangladesh. Data were collected using structured questionnaires, in-depth interviews, and focus group discussions. Chi-square tests were employed to ascertain associations.
... Milk contains a variable amount of estrogen (Pape-Zambito, 2010), which could conceivably affect monthly ovulation depending on the actual estrogen concentration and the amount of milk consumed. Another study showed that meat consumption has a profound effect on twinning rates (Steinman, 2006a). ...
The Amish are known for their high fertility and large families, but the Amish twinning rate has been of less interest. In an article published in 1970 (over 50 years ago), Cross and McKusick determined the Holmes County, Ohio, Amish twinning rate to be 15.3 twin pairs per 1,000 live births, which ranked among the highest known twinning rates at that time, while the U.S. national twinning rate hovered at around 9 per 1,000 per year. Within a few decades following the Cross and McKusick study, the twinning rates of the American population increased dramatically, and surpassed the Amish twinning rates. This surge in the twinning rate among the general American population was generally accredited to the widespread use of medically assisted reproduction (MAR), which favors multiple births, and the increased birth rates for older women, who have a significantly higher rate of multiple births. Holmes County has eight different Amish sects, ranging from fairly progressive to ultraconservative, and the five largest ones were the subjects of this study. The twinning rates of the different groups vary, parallel with degree of conservatism. The New Order Amish (most progressive) have a twinning rate of 20.1 twins per 1,000 births, whereas the Swartzentruber Amish have a rate of 34.5. Since all the groups are of identical ethnic stock and share virtually identical historical experiences, these twinning variances are difficult to explain, but may be due to diverging dietary practices that paralleled the conservative fragmentation.
... The prevalence of multiple pregnancies, especially twin pregnancies, continues to rise due to wider availability of in-vitro fertilisation (IVF). 1 In contrast, spontaneous conception of twins is a rarity compared to IVF conception, however, there is evidence that high consumption of red meat and a maternal history of twin gestation are associated with spontaneous conception of twins. 2 Conduct in a twin delivery continues to be one of the most challenging aspects of obstetric practice 3,4 and the optimal mode of delivery remains elusive. 5 There is an abundance of literature demonstrating that women carrying a twin pregnancy experience higher rates of complications during pregnancy and delivery compared to their counterparts carrying a singleton pregnancy. ...
Introduction: Appropriate intrapartum conduct in a twin delivery remains a challenging aspect of obstetric practice. The objective of this study was to compare neonatal and maternal outcomes in twin pregnancies according to mode of delivery.
Materials and methods: This is a single centre retrospective cohort study of all consecutive spontaneously-conceived twin deliveries (≥ 24 weeks, estimated fetal weight ≥ 500 grams) over a nine-year period between 01/01/2007 - 31/12/2016 at a tertiary-level centre. Neonatal outcomes included survival, APGAR score, prematurity-associated pathology (PAP), admission to the neonatal intensive care unit (NICU) and length of stay (LOS). Maternal outcomes included postpartum complications and LOS. Statistical analysis comprised Chi-square test with subsequent p-value and odds-ratio with 95% confidence interval. Statistical significance was set at p <0.05.
Results: A total of 173 consecutive women with spontaneously-conceived twin deliveries were enrolled in this study, 129 (74.6%) women delivered by caesarean section (CS). The success rate of vaginal delivery (VD) was 93.6% (44/47). A strong statistical correlation
was identified between CS and NICU admission; 53.2% vs. 1.5% (p=0.0001). Neonatal LOS in the NICU was significantly longer in the CS group. Prematurity-associated pathology (PAP) was noted in 75 pairs of twins (75/173); 61 pairs were delivered by CS, bearing strong statistical significance (p<0.0001). Postpartum complications occurred in 14.7% of CS compared to 13.6% of VDs.
Conclusion: Neonates delivered by CS had a higher rate of PAP, NICU admission, lower birth weight and longer LOS. This study
showed that VD is safe, especially when the first twin is in cephalic presentation.
... Even hormone levels in so called "organic" cows have levels high enough to influence hormone related conditions including acne, reproductive dysfunction, premature puberty, and higher rates of twins [86][87][88][89] . In looking at cancer in particular, the concern lies with the effects of growth hormones in addition to sex steroid hormones [90] . When considering that cow milk is meant to cause a calf to gain a couple hundred pounds within a few months, it makes sense that a lifetime of human exposure to those growth factors could contribute to developing cancer, and particularly hormone sensitive tumors [91,92] . ...
... In addition to nutritional status, basic genetics is also a key factor in the occurrence of twin births, as a plethora of research has shown that in humans and OWMs, females that have descended from lineages with a history of fraternal twinning are more likely to pro-duce fraternal twins than the females that have descended from lineages in which a history of fraternal twinning is absent (Geissmann 1989;Steinman 2006). In addition, repeated births of twins by the same mother or sired by the same father have been reported in some OWM colonies (Geissmann 1989). ...
The birth of twins, and especially multiple sirehood dizygotic twins, is very rare in Old World monkeys, the only previous record is of a captive rhesus macaque (Macaca mulatta). Here, we report a case of multiple sirehood dizygotic twins among the 114 newborns (0.88%) recorded in a population of semi-wild stump-tailed macaques (M. arctoides) in the Khao Krapuk Khao Taomor (KKP) Non-hunting Area, Thailand. Using ten microsatellite markers, we determined that the infants were sired by different adult males, thus suggesting the multiple sirehood. Since the association between twin birth and high frequencies of supernumerary (> 2) nipples was reported in Formosan macaques (M. cyclopis) in Taiwan, the supernumerary nipples were observed in KKP macaques. Of the 332 monkeys counted, 22% of the adults and subadults in the KKP population, and 33.3% of females in the focus (Ting) group, had supernumerary nipples. However, both twins and their mother had two ordinary nipples. Thus, we conclude that it has no association between the occurrence of supernumerary nipples and twin births in stump-tailed macaques.
... Although genetic selection against those individuals and breeds predisposed to twinning is relatively practical, many of the other associations with twinning, such as high milk production at the time of breeding, season of mating and parity, are clearly not. Interestingly, in humans dizygotic twinning appears associated with elevated levels of insulin growth factor (Steinman 2006), and there are likely dietary influences that may allow preventative strategies to be developed in future. ...
Placental retention is a common disease of periparturient dairy cows. Despite being well recognised, the exact aetiologies have not been fully elucidated. There is strong evidence of involvement of immune, hormonal and mechanical components in the pathogenesis of the disease, and in most cases more than one of these components contributes. Increased risk of retained placenta has been associated with reproductive disease including dystocia, Caesarean section, abortion, stillbirth and twinning, as well as other periparturient disease such as hypocalcaemia, negative energy balance and micronutrient deficiency. Major histocompatibility complex compatibility between the dam and calf also increases risk. Prevention should focus on responsible breeding programmes and control, where possible, of associated risk factors. Best practice for the treatment of individual animals remains contentious, but a targeted systemic antimicrobial therapy of only those animals demonstrating pyrexia or systemic illness is an approach supported by the research. Manual removal of foetal membranes has little evidence to support its efficacy and may well be detrimental to animal health.
... The twin-study approach, while attractive for its parsimony and for its ability to factor out, if not explicitly account for, environment, leaves open some important threats to validity when applied in sociological domains. The U.S. twinning rate, for example, climbed 65 percent between 1980 and 2002: a large increase in the number of DZ twin births attributable, at least in part, to environmental factors such as increasing maternal ages during pregnancy, the use of reproductive technologies, and maternal diet (Martin et al. 2003: 21ff; Steinman 2006). We know little about how families of these DZ twins may differ from the families of singleton children. ...
Growing interest in the genetic contribution to human behaviors has led to the growth of the field of behavioral genetics. The authors consider the concept of "environment" in behavioral genetics and argue that sociology is in a unique position to evaluate and specify a theo-retically robust concept of environment. Building on insights from classi-cal and contemporary social theory, the authors argue that the study of genetic influence on behavior needs to incorporate sociological understand-ings of contextual effects. The authors propose five points for evaluating behavioral genetic studies' conceptualization of environment and use those points to evaluate three exemplary recent studies. Keywords: genetics; environment; behavior; ontology When, in June 2005, Oprah Winfrey told a Johannesburg crowd that she felt "so at home" there because "I went in search of my roots and had my DNA tested, and I am Zulu," observers had every right to be skeptical, as some were (BBC News, June 15, 2005). Although the BBC and the South African Mail and Guardian (Lem-mer 2005) pilloried the unlikely specificity with which Oprah claimed her roots, 1 most American news outlets accepted the genetic basis of her contemporary com-fort (not to mention the accent: "'I'm crazy about the South African accent,' she said. 'I wish I had been born here.'") without serious question. Although DNA probably plays some role in her comfortable experience in South Africa, social and historical factors are presumably much more important in this case. Winfrey's pronouncement is only a particularly visible example of the increas-ing attention potential genetic origins for behavioral outcomes are enjoying in the popular press (Finkler 2000). Of particular recent importance is the likelihood that many human behavioral traits are, in part, genetically based. This possibility is the purview of the emerging discipline of behavioral genetics (Burgess 2005).
... There are familial and ethnic relationships with DZ twinning frequency, for example Nigerians have a relatively high rate of 1:11 compared to the Japanese at 1:250 (LeszczynskaGorzelak et al., 2000). The high rate in Nigerians has been postulated to be an environmental influence of elevated estrogen with yam consumption coupled with high dairy intake modulating insulin growth factor 1 (IGF-1) (Steinman, 2006). Familial (Machin, 2009) and ART factors are also implicated in monozygotic (MZ) twinning. ...
For decades the relationships of twinning and alterations in body patterning, such as laterality and asymmetry, have been investigated. However, the tools to define and quantify these relationships have been limited and the majority of these studies have relied on associations with subjectively defined phenotypes. The emerging technologies of 3-dimensional (3D) facial scanning and geometric morphometrics are providing the means to establish objective criteria, including measures of asymmetry, which can be used for phenotypic classification and investigations. Additionally, advances in molecular epigenetics provide new opportunities for novel investigations of mechanisms central to early developmental processes, twinning and related phenotypes. We review the evidence for overlapping etiologies of twinning, asymmetry and selected monogenic and complex diseases, and we suggest that the combination of epigenetic investigations with detailed and objective phenotyping, utilizing 3D facial analysis tools, can reveal insights into the genesis of these phenomena.
... Against this background, WHO and UNICEF are joining forces, and have developed the Global Immunization Vision and Strategy 2006-2015 (GIVS). 9 Both the World Health Assembly, 10 and UNICEF's Executive Board 11 recently welcomed the GIVS document as the framework for strengthening national immunisation programmes in the next decade. GIVS outlines four major strategic areas; we discuss each in turn. ...
... After undergoing a progressive decline, the twinning rates reversed in the late 1970s and have increased significantly in industrialized countries, and this has raised considerable concern (Pison & D'Addato, 2006). These phenomena were possibly related to demographic features such as maternal childbearing age, birth control, and assisted reproductive technologies (Eriksson & Fellman, 2004;Olsen, 2001;Steinman, 2006;Wilcox et al., 1996). The influence of factors such as lifestyle, nutrition, and economic status on twinning rates remains poorly understood. ...
Based on the birth record data from the National Vital Statistics in the 1990 Census of China, the present study analyzed the differences between urban and rural areas on monozygotic (MZ) and dizygotic (DZ) twin rates by maternal age in 1989. The twins by zygosity were calculated with Weinberg's differential method. Results show that the MZ and DZ twinning rates in China were associated with maternal age and that there were substantial differences between urban and rural areas. The MZ twinning rates in urban and rural areas were 2.36 pairs and 2.11 pairs per 1000 deliveries respectively, significantly lower than that in most studied populations. Furthermore, our analysis indicated that MZ twinning rates remained relatively constant for mothers under the age group of 36 to 38 years, but rose over this age group in both areas, albeit with a different slope. The DZ twinning rates were strikingly affected by maternal age, but the age for peak DZ rates was found within the age group of 33 to 35 years. In all maternal age groups except for 24 to 26 years, the DZ twinning rates in urban areas were higher than in rural areas. It remains unclear as to why the DZ twinning rates reversed to reach higher values within the older maternal age groups in China, but it is almost certain that the high twinning rates had nothing to do with in vitro fertilization.
... Two studies have recently reported that milk intake during pregnancy results in higher birthweight offspring [23,24]. The rise in IGF-1 with milk consumption may increase rates of twinning [25]. ...
Nutrients, hormones and growth factors in dairy foods may stimulate growth hormone (GH), insulin-like growth factor I (IGF-I), and raise the ratio of IGF-I to its binding protein, IGFBP-3. We conducted pilot studies in Mongolia and Massachusetts to test the extent to which milk intake raised somatotropic hormone concentrations in prepubertal children.
In Ulaanbaatar, we compared plasma levels before and after introducing 710 ml daily whole milk for a month among 46 10-11 year old schoolchildren. In a randomized cross-over study in Boston, we compared plasma hormone levels of 28 6-8 year old girls after one week of drinking 710 ml low fat (2%) milk with their hormone levels after one week of consuming a macronutrient substitute for milk.
After a month of drinking whole milk, Mongolian children had higher mean plasma levels of IGF-I (p < 0.0001), IGF-I/IGFBP-3 (p < 0.0001), and 75th percentile of GH levels (p = 0.005). After a week of drinking low fat milk, Boston girls had small and non-significant increases in IGF-1, IGF-1/IGFBP-3 and GH.
Milk drinking may cause increases in somatotropic hormone levels of prepubertal girls and boys. The finding that milk intake may raise GH levels is novel, and suggests that nutrients or bioactive factors in milk may stimulate endogenous GH production.
Natural selection should favour litter sizes that optimise trade-offs between brood-size and offspring viability. Across the primate order, the modal litter size is one, suggesting a deep history of selection favouring minimal litters in primates. Humans, however – despite having the longest juvenile period and slowest life-history of all primates – still produce twin births at appreciable rates, even though such births are costly. This presents an evolutionary puzzle. Why is twinning still expressed in humans despite its cost? More puzzling still is the discordance between the principal explanations for human twinning and extant empirical data. Such explanations propose that twinning is regulated by phenotypic plasticity in polyovulation, permitting the production of larger sib sets if and when resources are abundant. However, comparative data suggest that twinning rates are actually highest in poorer economies and lowest in richer, more developed economies. We propose that a historical dynamic of gene–culture co-evolution might better explain this geographic patterning. Our explanation distinguishes geminophilous and geminophobic cultural contexts, as those celebrating twins (e.g. through material support) and those hostile to twins (e.g. through sanction of twin-infanticide). Geminophilous institutions, in particular, may buffer the fitness cost associated with twinning, potentially reducing selection pressures against polyovulation. We conclude by synthesising a mathematical and empirical research programme that might test our ideas.
Natural selection should favor litter sizes that optimize trade-offs between brood-size and offspring viability. Across the primate order, modal litter size is one, suggesting a deep history of selection favoring minimal litters. Humans, however---despite having the longest juvenile period and slowest life-history of all primates---still produce twin-births at appreciable rates, even though such births are costly. This presents an evolutionary puzzle. Why is twinning still expressed in humans despite its cost? More puzzling still, is the discordance between the principal explanations for human twinning and extant empirical data. Such explanations propose that twinning is regulated by phenotypic plasticity in polyovulation, permitting production of larger sib-sets if-and-when resources are abundant. However, comparative data suggest that twinning rates are actually highest in poorer countries and lowest in developed economies. We propose that a historical dynamic of gene-culture coevolution might explain this geographic patterning. Our explanation distinguishes geminophilous and geminophobic cultural contexts, as those celebrating twins (e.g., through material support) and those hostile to twins (e.g., through sanction of twin-infanticide). Geminophilous institutions, in particular, may buffer the fitness cost associated with twinning, potentially reducing selection pressures against polyovulation. We conclude by synthesizing a mathematical and empirical research program that might test our ideas.
The phenomenon of twinning has fascinated humans from time immemorial. For example, Greek mythology describes twins who were fathered separately by two individual men. With the advent of chromosomal research, the existence of such a phenomenon has been elucidated and substantiated. Medical care of a naturally conceived twin pregnancy often entails attention to special issues that are not often encountered in singleton gestations. This presentation will emphasize many of the special issues which may come to the fore in dealing with the etiology and successful completion of natural multifetal gestations, in contrast to pregnancies initiated with the aid of laboratory, pharmaceutical, or surgery-based procedures. What makes obstetrics a uniquely different specialty is that the practitioner must continuously take into account the status of two classes of patients at the same time: the gravida and her babies. This is true throughout the pregnancy as well as during labor & delivery.
The etiologies of monozygotic (one egg) twins (MZ) versus dizygotic (two eggs) twins (DZ) are significantly different. MZ twins result from the splitting in half of a single fertilized egg, whereas DZ twins are separate pregnancies beginning in the same menstrual cycle.
The first universal birth registry of children was initiated in Nordic countries in the 17th century. In Sweden and Finland it was officially introduced in 1749. Since then, the prevalence of twin pregnancies has been estimated in these countries. It turned out that the proportion of twin pregnancies was relatively constant until the end of the 19th century. Since 1900, the decreasing occurrence of twin pregnancies has been recorded in most European countries and the US. This trend remained present until the end of the 1970s, when a reverse tendency was observed and lasts until today.
In the last three decades, all over the world we have been observing a distinct increase in the number of twin pregnancies. The causes of this phenomenon can be found not only in the wider and more effective application of artificial procreation methods. At present, one of the most important natural factors responsible for the increase of this percentage is the raise in the age of women starting motherhood. This influence seems to have an impact in two aspects; at first - with age there is an increase in the frequency of idiopathic multiple pregnancies; second - there is a natural decrease in fertility related to the ageing of ovaries, and also the presence of disorders reducing women's fertility, such as e.g. sexually-transmitted infections, uterine myoma or endometriosis, what in turn increases the necessity to apply techniques of supported reproduction and consequently an increase in the percentage of iatrogenic multiple pregnancies.
The aim of the review was to describe changes in some chemical components of milk during mastitis. Udder inflammation causes a decrease or increase in biologically active milk components, dependent on the clinical course of the inflammation and its etiological agents. Examinations performed over the last years have mainly focused on cytokines, acute phase proteins, eicosanoids, enzymes and caseinolysis products. The increase of pro-inflammatory cytokines: TNF-α, IL-1β, IL-6, GM-CSF, IL-8, and 11-12 has always been noted in acute forms of mastitis, and is related to an increase of IGF and TGFs, acute phase proteins and bacterial and leukocyte enzymes activity. In mild cases where inflammations are caused by Staph. aureus or Str. uberis, changes in cytokines or growth factors have occurred later and have been less intense. A decrease of casein, lactoalbumin-α, lactoglobulin-p, and vitamins E and C, and triiodothyronine in mastitic milk have also been stated. The increase in NAGase, LDH, serum amyloid A and haptoglobin can indicate both the beginning and intensiveness of the inflammatory process in the mammary gland. Antibacterial components of milk: lactoferrin, lysozyme and lactoperoxidase-thiocyanate- hydrogen peroxide systems do not inhibit bacteria in the inflamed secretion. However, they can indicate the false-positive results of screening tests for antibiotic residues in milk. Somatic cells, bacterial proteases and lipases together with endogenous enzyme plasma hydrolyze casein, gelatin, collagen, hemoglobin, and lactoferrin and secretor cell proteins. The decrease of α-casein, β-casein and lipids and increase of κ-casein, protease-peptones and free fatty acids is due to the effect of the inflammatory enzyme's activity. Independently of bacterial toxins, the presence in fresh milk of higher concentrations of TNF-α and other cytokines, PGF2-α, IGF, BSA, histamine, bradykinin, thiocyanate or lower concentrations of β-casein, lactoalbumin-α, lactoglobulin-p, vitamins E and C or triiodothyronine, that are connected with mastitis can be potentially detrimental both for the health of calves and, above all, for humans.
Learn to accurately diagnose, prevent and treat all three acnes using both traditional and novel approaches to understanding the causes and selecting the most effective treatments. Acne vulgaris is an extremely common condition. It is troublesome to manage, often persisting into middle age. Exact causes are becoming clear and include several hormonal stimulants, some triggered by the Western diet, and a pathogen ignored for decades. Acnes rosacea and inversa (hidradenitis suppurativa) are discussed from entirely new viewpoints. Acne: Causes and Practical Management will provide readers at all levels with a practical, well-illustrated approach to fully understanding these disorders; a faster and more cost-effective management regimen and the rationales for their prevention. In full colour throughout and with over 200 excellent clinical images, key highlights include: Full coverage of all acne presentations - acne vulgaris, acne rosacea and acne inversa (hidradenitis suppurativa) An integrated view of the causes of the varied and overlapping acnes Preventive, novel and curative approaches to treatment Medical, surgical, and dietary components of management, fully integrated Highly practical focus on prevention, treatment and prophylaxis based on emerging pathogenetic conceps. Brought to you by one of the world's leading authorities on the subject, Acne: Causes and Practical Management will be a valuable re-education for the dermatologist and all those who treat or suffer from these three conditions.
At present, we do not understand how human handedness arose. Although much attention has been paid to several genetic theories, some studies involving twins have indicated that the influence of genetic and environmental factors on handedness may be minimal or nonexistent.
The incidence of left-handedness amongst males is higher than with females, according to a large body of research. People who are ambidextrous are more likely to start to write with their right hand, even when they are not forced to do this. The left hemisphere of the brain is also lateralized when compared to the right hemisphere and vice versa.
Our research examined handedness in dizygotic and identical monozygotic twins in Koya Town/ Erbil governorate. In 2014, we mailed a questionnaire to 100 twins aged between 18 and 50 to survey their handedness. The survey determined whether each subject was a monozygotic or dizygotic twin, and then questioned them about their handedness. We examined whether both twins had the same handedness or different handedness, and whether individual twins have a higher prevalence of left-handedness or right-handedness.
The results revealed that in 62% of cases, both monozygotic twins in a pair are right-handed. On the other hand, both dizygotic twins are right-handed only 54% of the time. Furthermore, dizygotic twins are more likely to have one left-handed and one right-handed twin when compared to monozygotic twins. We also found that the prevalence of right handedness in individual monozygotic twins regardless of the handedness of the other twin was 77%, whereas the prevalence of left-handedness was only 21%. The remaining 2% of monozygotic subjects were ambidextrous.
These results indicate that unique genetic and environmental factors may account for the majority of variance in that is observed in handedness, although the relationship between the brain, handedness, environmental effects and genetic effects is a complex one. This is a view that is corroborated by a number of recent neuroscientific and genetic studies that are examined in this article.
The mystery of human lateralization in human
To examine the rate of spontaneous twinning in selected countries in order to evaluate the impact of environmental stress and related socioeconomic factors on balancing reproductive activity and longevity.
Four countries with similar ancestry were considered, 2 in Africa and 2 in the Caribbean. Data on gross domestic product per capita, as a measure of indigenous conditions, access to proper diet, health care, sanitation and shelter were compared with the relative rate of twinning.
The data show an inverse relationship between wealth and environmental conditions, and the incidence of multiple gestations.
Through goods and services, improved living conditions reduce environmental stress and its adverse effect on the balance of biologic reproduction vs. longevity. In addition, breast-feeding, as a social expression and an economic easement, correlates with the chance of conceiving twins in a subsequent pregnancy. It would thus appear that the twinning rate can be taken as a barometer of the population's biologic attempt to perpetuate its gene pool expeditiously when an existential threat occurs.
Over the last decades, there has been a twin boom in terms of live births. Meanwhile, new insights into the genetics of twinning have changed major paradigms. The first major paradigm is that monozygotic (MZ) twins are identical. The second is that twins are either MZ or dizygotic (DZ). The third is that MZ twins happen by chance alone. We have discovered striking epigenetic and other differences between seemingly alike individuals; the presence of fascinating intermediate twin forms; and the potential for familial MZ twinning and even a twinning gene. As this article discusses, the aforementioned paradigm shifts have influenced novel research directions and improved clinical approaches to twin-management.
To evaluate the possibility of male-line inheritance of dizygotic twinning potential.
Women with multiple births who had previously volunteered to participate in studies in this series were asked about the frequency of males genetically related to the index mother's husband who had also fathered multiples. Only spontaneous gestations were considered.
If male involvement in twin pregnancies were entirely random, <1% would have had male relatives who had also fathered multifetal gestations. However, 30% were found to have such relatives in the families evaluated here.
These results suggest that the capability to father multiples (twins or higher) spontaneously is, in many cases, an inherited trait along the male line--i.e., the male factor in twinning. Producing multiples requires not only women able to doubly ovulate but also men capable of supplying active sperm that could fertilize >1 egg in a given cycle.
To evaluate the relationship of maternal height to the rate of twinning and the possible connection of these parameters to the coexistent level of insulinlike growth factor (IGF).
Since spontaneous multiple gestations in humans are relatively uncommon in general, it is reasonable to consider distin guishing physical attributes such as height, that may have some functional relationship to this phenomenon. In a prior study, hereditary and dietary factors affecting the level of IGF were found to correlate with the rate of twinning. In that height is known to parallel the serum level of IGF, a survey of women who had previously conceived spontaneously and had given birth to twins or triplets was undertaken. Their heights were compared with the mean value for the general female population,
Mothers of 129 sets of spontaneous multiples displayed a mean height of 164.8 cm as compared to 161.8 cm for the general population of women (p < 0.005).
These data confirm those from previous studies and corroborate the proposed relationship between maternal height and the rate of twinning. Thus, the results reported here further support the IGF model of twinning.
To determine whether concentrations of insulin-like growth factor-1 (IGF-1) in blood of ewes change during the oestrous cycle, oestrus was synchronized for 45 ewe lambs from four genotypes (Finn ewes selected for low ovulation rate (LF), Finn ewes selected for high ovulation rate (HF), unselected control Finn ewes (CF) and Cambridge ewes (CAM)) using progestin sponges and blood samples were taken every day from day 0 (day 0 = day of progestin sponge removal) to day 5, and then every second or third day until 3 days after the next oestrus. Ovulation rates (determined via laparoscopy) following the first oestrus were 1.3, 3.3, 2.0 and 2.1 for LF, HF, CF and CAM groups, respectively. In a second experiment, jugular and utero-ovarian venous blood samples were collected simultaneously from seven Rambouillet crossbred ewes during the mid-luteal phase of an oestrous cycle to determine whether the ovary is a major source of blood IGF-1. In the first experiment, plasma IGF-1 concentrations increased (P < 0.05) between days 0 and 3, and then decreased (P < 0.05) between days 4 and 8 in all groups. IGF-1 concentrations increased again at the subsequent oestrus. There was no significant difference in plasma IGF-1 between HF and LF ewe lambs. Overall, plasma IGF-1 was lowest (P < 0.05) in CAM and highest in CF ewe lambs at all stages. Plasma IGF-1-binding protein activity did not vary with stage of cycle or differ (P > 0.10) among genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)
The present EU moratorium banning the use of bST to increase milk yield implies the need for official controls. Our study aimed to identify milk from bST treated cows via the induced increase of insulin-like growth factor 1 (IGF-1) concentrations. A non-extraction radioimmunoassay for IGF-1 was improved and thoroughly validated for milk. Accuracy was 99% recovery in a fortified sample material, the precision was 5.1% intra-assay variation and 13.4% inter-assay variation. Parallelism was proved by a dilution experiment which yielded a regression line with a slope (-0.7%) not significantly different from zero (P = 0.534). Naturally occurring milk IGF-1 levels were recorded in 5777 random milk samples from the Bavarian dairy cow population. In samples from lactation week 7 to 33, the effect of somatic cell count (SCC), protein content and parity could be quantified and corrected; thus a normal distribution (-0.068 mean +/- 0.440 s) of the corrected logarithmic IGF-1 levels (corr ln IGF-1) was obtained. IGF-1 concentrations occurring in milk from bST treated cows were recorded in 33 Brown Swiss cows treated once with rbST (POSILAC). Mean corr in IGF-1 levels increased by 0.828 and 0.477 in first parity and older cows, respectively. Thus 60% and 29%, respectively, of the positives could be detected at a 95% probability. If our results are confirmed in experiments with more bST treated cows and with prolonged treatment intervals. IGF-1 measurements might be useful to monitor for bST application in milk samples.
Nutritionally induced anovulatory and cyclic Angus x Hereford heifers were used to evaluate follicular growth and concentrations of hormones and metabolites during anovulation and resumption of ovulation. Anovulatory heifers were fed to gain 0.6 (LGAIN) or 1.5 (HGAIN) kg/day until resumption of ovulation, and heifers with normal estrous cycles were fed a maintenance diet (M). Follicles >/= 4 mm in diameter were measured by daily ultrasonography in HGAIN and LGAIN heifers during one follicular wave before realimentation (Wan) and in two waves (W-2, W-1) immediately before the wave resulting in first ovulation or luteinization (W0). Ovaries of M heifers were evaluated to determine the day of ovulation of the second-wave dominant follicle (DF). Resumption of ovulation after realimentation occurred 23 days earlier in HGAIN than in LGAIN. Maximum diameter, growth rate, and persistence of dominant follicles increased, while persistence of first subordinate follicles decreased between anovulation and resumption of ovulation in anovulatory heifers. Concentrations of LH in serum were similar for HGAIN and LGAIN and gradually increased during realimentation. The increase in estradiol before the first ovulation was less in realimented heifers compared with cyclic heifers. Concentrations of insulin-like growth factor-I (IGF-I) in HGAIN and LGAIN gradually increased during realimentation but were lower than concentrations of IGF-I in cyclic heifers at ovulation. Increased diameter, growth rate, and persistence of the DF were associated with increased concentrations of LH, estradiol, and IGF-I during the transition from nutritionally induced anovulation to resumption of ovulatory cycles.
Mean serum insulin-like growth factor-I was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone.
In order to explore the association between multiple birth risk and diet, data were analysed from a case-control study on risk factors for multiple births conducted in Italy between 1988 and 1998. A total of 185 cases (median age 30 years) were interviewed: 36 women delivered monozygotic and 149 delivered spontaneous dizygotic multiple births. The control group comprised 498 women who gave birth at term (>37 weeks gestation) to healthy infants on randomly selected days at the same clinic. Women were specifically excluded if they reported a history of multiple pregnancy or they had received treatment for infertility for the index pregnancy. No marked differences emerged in daily intake between cases and controls and a total of 35 foods items, including the major sources of beta-carotene, retinol, ascorbic acid, vitamin D, E, methionine folate and calcium in the Italian diet. Likewise intake of selected micronutrients was largely similar in dizygotic cases, monozygotic cases and controls, with the only exception of a slightly lower intake of folates in dizygotic pregnancies in comparison with controls: this difference was statistically significant (P < 0.05), but limited in quantitative terms (mean daily intake of folate 192.4, 183.2 and 191.4 microg respectively in monozygotic, dizygotic cases and controls). In conclusion, the results of this study do not support the role of diet in the development of multiple births.
Experiments were carried out to investigate putative beneficial effects of adding epidermal growth factor (EGF) or insulin-like growth factor-I (IGF-I) for bovine embryo culture in chemically defined media. Presumptive zygotes (18 h post-insemination) were randomly assigned to culture treatments. In experiment 1, treatments involved additions of recombinant human EGF to provide concentrations of 0 ng (control), 1, 5, and 25 ng/ml. No differences were seen in numbers of 4-cell stage embryos between groups. A concentration of 5 ng/ml EGF but not 1 or 25 ng/ml during embryo culture improved percentages of 4-cell stage embryos reaching blastocysts compared to the control (P<0.05). Numbers of inner cell mass (ICM) cells and trophoblast cells of day 8 blastocysts were similar for the control and 5 ng/ml EGF-treated groups. In experiment 2, culture with recombinant human IGF-I in concentrations of 0 ng (control), 2, 10, and 50 ng/ml resulted in no differences in numbers of 4-cell stage embryos between groups. When compared to controls, IGF-I treatments at 10 and 50 ng/ml improved proportions of 4-cell stage embryos that reached blastocysts (P<0.05). In experiment 3, numbers of ICM cells of day 8 blastocysts were significantly higher after being cultured with 50 ng/ml of IGF-I compared to those of the controls (P<0.05). No additive effect of combining EGF (5 ng/ml) and IGF-I (50 ng/ml) was seen when results were compared to those following supplementation of the media with either EGF or IGF-I alone. In conclusion, both EGF and IGF-I could independently enhance bovine preimplantational development in chemically defined media and IGF-I but not EGF may play a mitogenic role during early bovine development.
To examine whether a high protein intake (PI) from either milk or meat, at a level often seen in late infancy, could increase s-IGF-I and s-IGF-I/s-IGFBP-3 in healthy, prepubertal children. IGF-I levels are positively associated with growth velocity in children and some studies suggest that a high animal PI can stimulate growth. During protein deprivation IGF-I decrease, but it is unknown whether a high PI can increase s-IGF-I in well-nourished children.
In all, 24 8-y-old boys were asked to take either 1.5 l of skimmed milk (n = 12) or the same amount of protein as 250 g low fat meat (n = 12) daily for 7 days. The remaining diet they could choose freely. At baseline and after 7 days, anthropometrical variables were measured, diet was registered (3-day weighed records), and s-IGF-I and s-IGFBP-3 (RIA) were determined after fast.
PI increased by 61% in the milk group to 4.0 g/kg/day (P < 0.0001) and by 54% in the meat group to 3.8 g/kg/day (P = 0.001). The high milk intake increased s-IGF-I by 19% (P = 0.001) and s-IGF-I/s-IGFBP-3 by 13% (P < 0.0001). There were no increases in the meat group.
High intake of milk and not meat, increased concentrations of s-IGF-I and s-IGF-I/s-IGFBP-3 significantly. Compounds in milk and not a high PI as such seem to stimulate IGF-I. This might explain the positive effect of milk intake on growth seen in some studies.
Recent studies have implicated insulin-like growth factor I (IGF-I) as an intraovarian regulator of follicular growth and differentiation. Therefore, we investigated the possibility that cattle selected for twin births may have increased concentrations of IGF-I within the ovarian follicle and(or) in peripheral blood. The estrous cycles of 14 cows with histories of producing twins and 12 control monotocous cows were synchronized with 35 mg of prostaglandin F2 alpha (PGF2 alpha). Blood and follicular fluid were collected 48-50 h post-administration of PGF2 alpha (follicular phase of the estrous cycle). Concentrations of IGF-I were measured by RIA after acid-ethanol treatment of serum or follicular fluid. Twin-producing cows had a greater (p less than 0.05) number of large (greater than or equal to 4 mm) follicles and 47% greater (p less than 0.05) concentrations of IGF-I in peripheral blood than control cows. Cattle selected for high twinning frequency also had greater (p less than 0.05) concentrations of IGF-I (+/- SE) in the two largest follicles than control (unselected) cows (327 +/- 28 vs. 243 +/- 29 ng/ml). IGF-I concentrations in pooled small (1-3.9 mm) follicles were less (p less than 0.05) than in large follicles but did not differ between control and twin-producing cattle. In addition, the percentage of IGF-I concentrations measured in follicular fluid to that of serum was lower (p less than 0.05) in small follicles than in large follicles, and was greater (p less than 0.05) in large follicles of control (93.2 +/- 5.3%) than twin-producing (76.2 +/- 4.4%) cattle.(ABSTRACT TRUNCATED AT 250 WORDS)
Six lactating, non-pregnant Jersey cows were given subcutaneous injections of recombinantly derived bovine growth hormone for 7 d. Milk yield was increased by 4.5 kg/d on d 7, compared with the average yield of 10.7 +/- 0.4 kg/d (mean +/- s.e.m.) for the 7 d preceding treatment. Concentrations of insulin-like growth factor I (IGF-I) in the milk increased from 0.44 +/- 0.04 nmol/l (mean +/- s.e.m.) during the 7 d preceding treatment to 1.6 +/- 0.2 nmol/l on d 7 of treatment. Taking the increase in milk yield into account the total increase in the secretion of IGF-I into milk of one udder half was 6-fold. Plasma concentrations of total IGF-I rose from 15.5 +/- 1.3 nmol/l (mean +/- s.e.m.) on the day preceding treatment to 56.9 +/- 3.6 nmol/l (mean +/- s.e.m.) on d 7 of treatment. Mammary plasma flow increased from 1.6 +/- 0.09 to 2.2 +/- 0.06 l/min.udder half over the same time. Estimates of the amount of IGF-I that reached the mammary gland gave values of 24 and 116 nmol/min.udder half before and during treatment respectively. IGF-I in milk of treated cows was associated predominantly with proteins ranging from 40,000 to 150,000 mol.wt, but a significant proportion (19%) of the total IGF-I was present in the free unbound form. IGF-I crosslinking studies revealed the presence in milk of one specifically labelled band at 31,000 mol.wt.
In Europe and the USA, both mean birth weight and age-standardized dizygotic twinning rates correlate positively and significantly with latitude. It seems possible that these two sorts of correlation have explanations in common via pituitary action. Factors which may be responsible for such action are total consumption of food and consumption of specific items of diet, for example, milk products and potatoes. Lastly, one might wonder whether the association of photoperiodicity with latitude is relevant.
Owing to the rarity of triplets and higher multiple births, most studies of multiple births have been focused on twins. One of the fields of study which has attracted considerable interest is the association of biosocial factors with twinning. Although much work has been done in this field in Caucasian populations, very little investigation has been carried out in tropical areas, some of which have the highest twinning rates on record. In this paper, the results of recent studies on twinning conducted in Aberdeen (Scotland) and Ibadan (Nigeria) will be presented to illustrate the influence of some biosocial factors on twinning.
A meaningful comparison of the twinning rates of different populations can be hindered by several factors that may influence the rates. Chief among these factors are the sources of data from which the rates are derived and the maternal age structure of the populations. The effects of such factors were minimal when the twinning rates of 14 ethnic groups in California were compared. After standardization for maternal age, twinning rates per 1000 maternities for the main ethnic groups were 13.20 for blacks, 10.05 for whites, and 7.18 for Asians. There were significant differences within the Asian group. The highest rate was for Cambodians (8.57). This rate compares with rates of approximately 6 for Koreans, Thai, and Vietnamese. These rates are similar to those found in Asia but lower than those for Californian Chinese, Japanese, and Filipinos, who have been established in the state for longer. In general, the results provide support for previous reports that twinning rates are modified by both migration and interethnic mixing. Rates for Indians from India were lower than those reported from the Indian subcontinent, whereas the twinning rates for Native Americans (10.15) and Pacific Islanders (10.60) were similar to the rate for US whites.
The morphology and number of cells in the trophectoderm (TE) and inner cell mass (ICM) of buffalo blastocysts derived from in vitro fertilization and cultured in the presence or absence of insulin-like growth factor-I (IGF- I) were analyzed by differential fluorochrome staining technique. The total cell number (TCN), TE number, and ICM cell number were significantly higher in blastocysts developed in vitro in the presence of IGF-I as compared to blastocysts developed without IGF-I (P < 0.01). It was observed that the buffalo blastocyst took 5-9 days postfertilization to develop in vitro. In order to correlate the time required for blastocyst development and the allocation of cells to TE and ICM, blastocysts were designated as fast (developing on or before day 7) or slow (developing after day 7). The TCN, TE, and ICM cells of fast-developing blastocysts cultured in the presence of IGF-I were significantly higher than slow-developing blastocysts (P < 0.01). The blastocysts developed on day 6 had a mean total cell number 118.6 ± 21.4, which significantly decreased to 85.6 ± 17.4, 62.0 ± 14.5, and 17.0 ± 4.0 on days 7, 8, and 9, respectively (P < 0.05). Normal development of buffalo embryo showed that, on average, embryos reached compact morula stage at the earliest between days 4.5-5.5. Blastocysts developed, at the earliest, between days 5.0-6.0, and it took them, on average, 6.5 days to hatch from the zona pellucida. TCN, TE, and ICM increased three times from morula to blastocyst; however, the proportion of ICM to TCN remained the same, in both embryonic stages. TE approximately doubled in hatched blastocysts, as compared to unhatched blastocysts (P < 0.05). However, ICM cells were decreased. The time required for development of parthenogenetic blastocysts was observed to be greater as compared to in vitro fertilized (IVF) blastocysts. The total cell number of parthenogenetic blastocysts was 100.8 ± 11.3, including 59.2 ± 8.4 cells of TE and 42.1 ± 6.9 cells of ICM.
Our purpose was to examine the regulation of fetal serum concentrations of insulin (C-peptide), insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, which are growth-regulating factors in the fetus, in monozygotic and dizygotic twin pairs.
Cord serum samples were collected from 110 twin pairs and compared with 178 nonsibling singleton pairs with the same gestational age. Five twin pairs were excluded from the statistical analyses because of severe intrauterine growth restriction and placental abnormalities in one. Zygosity was assigned by histologic examination of the placenta and by a questionnaire sent to the mother when the twins were > or = 6 months old. Analyses included the calculation of correlation coefficients, between-pair variation, and univariate genetic analysis.
Cord serum C-peptide concentrations were highly correlated in monozygotic (r = 0.94) and dizygotic twins (r = 0.79) but not in singleton pairs (r = -0.05); the between-pair variation was also smaller in twins than in singletons. Genetic analysis demonstrated a large contribution of the common environment to the variance in C-peptide concentrations (80%) and a smaller genetic contribution (12%). Insulin-like growth factor-I concentrations were better correlated in monozygotic (r = 0.82) than in dizygotic twins (r = 0.42), with a smaller between-pair variation in the former group (22% +/- 4% vs 51% +/- 5%). Univariate genetic analysis indicated that insulin-like growth factor-I levels were regulated predominantly by genetic mechanisms (93% in boys and 77% in girls). The regulation of insulin-like growth factor-II was more complex, with a gender-specific genetic contribution (50% for both sexes combined, 63% for girls but only 5% for boys). Insulin-like growth factor binding protein-1 was regulated by genetic mechanisms (41%) and the common environment (32%) but also by the specific or unique environment of each fetus (27%). In all five twins with intrauterine growth restriction of one member insulin-like growth factor binding protein-1 concentrations were markedly higher in the growth-restricted fetus.
Insulin secretion in twin fetuses is determined primarily by their common, probably maternal, environment, whereas insulin-like growth factor-I production is predominantly genetically regulated. Insulin-like growth factor-II and insulin-like growth factor binding protein-1 are regulated by both genetic and environmental factors. Of these growth-regulating factors, insulin-like growth factor binding protein-1 appears to be the best marker of intrauterine growth restriction in the individual case.
The possibility of oral delivery of recombinant human insulin-like growth factor-I was investigated in rats. The degradation of ¹²⁵I-rhlGF-I in the gastrointestinal (GI) contents was in the order of jejunum = ileum >> large intestine, and little degradation was found in the stomach. Some adjuvants could inhibit the degradation, especially aprotinin and casein inhibited by 70-95%. On the other hand, rhlGF-I was relatively stable in the subcellular fraction of mucosal cells (BBM, cytosol, lysosome), and there was no site difference through the intestine. The bioavailability (BA) of rhlGF-I after oral administration was 9.3%, which was much greater than that of insulin. The BA was further increased by coadministration with aprotinin and casein, indicating that the stabilization of rhlGF-I in GI tract could enhance its absorption. From the results of gel filtration chromatography of rat plasma following oral administration of ¹²⁵l-rhIGF-I, the peaks in high molecular region were detected and they were thought to be macromolecular complexes which consist of ¹²⁵I-rhlGF-I and IGFBP-2 and/or -3. These results strongly suggest the possibility of oral delivery of rhlGF-I.
We also examined the absorption kin etics of rhlGF-I by the in situ single-pass perfusion method. The absorption clearance (CLa) of rhlGF-I was dependent on its concentration. Using acid-washing technique, rhlGF-I was found to be adsorbed acid-sensitively to the mucosal surface and the incorporation of immunoreactive rhIGF-I to the mucosal tissue was recognized at the same time. These results suggest that rhlGF-I is absorbed partly by a specialized absorption mechanism.
The galactopoietic actions of bovine somatotropin are both direct and indirect. Indirect actions are apparently mediated by the insulin-like growth factor (IGF) system. The objective of this study was to compare systemic (plasma) versus local (lymph) concentrations of IGF. Afferent mammary lymph most nearly represents the extracellular fluid that is bathing mammary tissue. Catheters were surgically implanted in the jugular vein and the superficial afferent mammary lymph vessels of four lactating cows. A crossover design was utilized to evaluate the effects of bovine somatotropin (bST). After 2 d of basal sampling, either bST (40 mg/d) or excipient was administered daily for 5 d. After the conclusion of the bST study, a second study was conducted in which cows were deprived of feed for 36 h. Blood and lymph were simultaneously sampled at least every 6 h throughout both studies. Milk yield was increased by bST, and concentrations of IGF-I were increased in plasma and lymph. The relationship between plasma and lymph concentrations for IGF-II, bST, insulin, glucose, urea nitrogen, and nonesterified fatty acids were similar during bST treatment. Milk yield was reduced 76% by 36 h of feed deprivation. Feed deprivation also caused a reduction of IGF-I in plasma, but concentrations of IGF-I in lymph were not altered. In contrast, changes in IGF-II, bST, insulin, glucose, urea nitrogen, and nonesterified fatty acids that were caused by feed deprivation followed similar patterns in plasma and lymph. Clearly, if IGF-I mediates the mammary actions of bST, then concentrations of IGF-I in plasma correlate with milk yield responses as well as, if not better than, concentrations in lymph.
To determine whether dietary counseling to increase milk intake could produce useful changes in the calcium economy and what, if any, other nutrition-related changes might be produced.
Randomized, open trial.
Two hundred four healthy men and women, aged 55 to 85 years, who habitually consumed fewer than 1.5 servings of dairy foods per day. Six academic health centers in the United States.
Subjects were instructed to consume 3 servings per day of nonfat milk or 1% milk as a part of their daily diets, or to maintain their usual diets, for a 12-week intervention period, which followed 4 weeks of baseline observations.
Energy and nutrient intake assessed from milk intake logs and 3-day food records; serum calciotrophic hormone levels at baseline and at 8 and 12 weeks; urinary excretion of calcium and N-telopeptide at 12 weeks.
Repeated-measures analysis of variance.
In the milk-supplemented group, calcium intake increased by 729 +/- 45 mg/day (mean +/- standard error), serum parathyroid hormone level decreased by approximately 9%, and urinary excretion of N-telopeptide, a bone resorption marker, decreased by 13%. Urine calcium excretion increased in milk-supplemented subjects by 21 +/- 7.6 mg/day (mean +/- standard error), less than half the amount predicted to be absorbed from the increment in calcium intake. All of these changes were significantly different from baseline values in the milk group and from the corresponding changes in the control group. Bone-specific alkaline phosphatase level (a bone formation marker) fell by approximately 9% in both groups. Serum level of insulin-like growth factor-1 (IGF-1) rose by 10% in the milk group (P < .001), and the level of insulin-like growth factor binding protein-4 (IGFBP-4) fell slightly (1.9%) in the milk group and rose significantly (7.9%) in the control group (P < .05).
The changes observed in the calcium economy through consumption of food sources of calcium are similar in kind and extent to those reported previously for calcium supplement tablets. The increase in IGF-1 level and the decrease in IBFBP-4 level are new observations that are beneficial for bone health. Important improvements in skeletal metabolism can feasibly occur in older adults by consumption of food sources of calcium. Dietitians can be confident that food works, and that desired calcium intakes can be achieved using food sources.
To investigate the possibility of insulin-like growth factor-I (IGF-I) as an adjunctive factor for ovulation induction.
The model of anovulatory mice was established by single injection of testosterone propionate. Thirty anovulatory mice were divided into 3 groups, each contained 10 mice. IGF-I 1 microgram + human menopausal gonadotropin (hMG) 5 IU, IGF-I 2 micrograms or hMG 10 IU alone was injected intraperitoneally to each group respectively. Cyclic changes of vaginal smear and numbers of oocytes in fallopian tubes were used to assess the effect.
Vaginal smears of 8 mice in IGF-I + hMG group, 6 mice in hMG group and 2 mice in IGF-I group returned to normal cyclic pattern. The differences between IGF-I + hMG group and IGF-I or hMG groups were significant (P < 0.01 and P < 0.05), but the difference between IGF-I group and hMG group was not significant (P > 0.05). The average numbers of oocytes within fallopian tubes were 12.3 in IGF-I + hMG group and 9.2 in hMG group (P < 0.05). In IGF-I group there were no oocytes in the fallopian tubes of two mice whose vaginal smears returned to normal.
IGF-I may be a potential agonist agent for ovulation induction.
Insulin-like growth factor (IGF)-I is present in the milk of various species. A prerequisite for any biological activity of milk-borne IGF-I in the suckling young is to survive the gastrointestinal luminal digestion. In the present study, the stability of IGF-I was examined in the gastrointestinal lumen in neonatal pigs.
Iodine-labeled IGF-I was incubated in the gastrointestinal luminal fluids of 3-day-old suckling and 45-day-old weaned pigs at 37 degrees C for 20 minutes. Degradation of the peptide was analyzed by trichloroacetic acid (TCA) precipitation, liquid chromatography, and receptor binding assay.
IGF-I remained unchanged in the gastric fluids of suckling and weaned pigs when determined by TCA precipitation. IGF-I degraded 3%, 18%, and 37% in the luminal fluids of the proximal, mid and distal small intestine in suckling piglets compared with 53%, 62%, and 54% in weaned pigs. The results were supported by the chromatography and receptor binding analysis. Porcine colostrum had a capacity to protect IGF-I from gastrointestinal luminal digestion in weaned pigs.
Milk-borne IGF-I is stable in the gastrointestinal lumen in suckling pigs and may play a role in regulating postnatal development in the suckling young.
Insulin-like growth factors (IGFs) are potent mitogens that have been implicated in control of growth and development during the perinatal period. These hormones are also present in biologically significant quantities in mammalian milks. Although one site of action of these IGFs may be at the intestinal level, current information about whether they pass intact into the circulation is conflicting.
To test the hypothesis that milk-borne IGFs are absorbed into blood in receptor-active form, suckling rats were given either recombinant human (rh)125I-IGF-I or -II (4 x 10(6) counts per minute [cpm]), and the activity present in portal and cardiac blood was examined at 5, 10, 20, and 30 minutes after ingestion for presence of appropriate molecular weight peptides in these samples. In selected samples, purified radioactive samples were tested for their ability to bind competitively to crude membranes bearing IGF receptors.
The results of these studies indicate that rh125I-IGF-I is absorbed in receptor-active form into the portal circulation and that maximal amounts are present 20 to 30 minutes after ingestion. Estimation of the presence of intact hormone was made on the basis of the elution profile of samples when run on gel chromatography as well as reversed-phase high-performance liquid chromatography. Isolated samples from portal blood also bound competitively to placental membranes bearing IGF receptors. In contrast, rh125I-IGF-II could not be demonstrated in receptor-active form in portal blood. Chromatography showed appropriate sized peaks with greater activity in portal than cardiac samples, but competitive binding was not appreciated.
It is likely that at least milk-borne IGF-I is absorbed intact and may exert effects on liver and other peripheral tissues. In addition, this study lends further credence to the possibility of an enterohepatic circulation for IGF-I.
An autosomal genome scan for quantitative trait loci (QTL) affecting twinning rate was carried out in the Norwegian Cattle population. Suggestive QTL were detected on Chromosomes (Chr) 5, 7, 12, and 23. Among these, the QTL positions on both Chr 5 and Chr 23 are strongly supported by literature in the field. Our results also confirm previous mapping of a QTL for twinning to Chr 7, but definitely suggest a different location of the QTL on this chromosome. The most convincing QTL peak was observed for a region in the middle part of Chr 5 close to the insulin-like growth factor 1 (IGF1) gene. Since IGF1 plays an important role in the regulation of folliculogenesis, a mutation search was performed by sequencing more than 3.5 kb of the gene in actual families. The sequencing revealed three polymorphisms in noncoding regions of the gene that will be important in fine structure mapping and characterization of the QTL.
African American children have greater bone mineral density (BMD) and bone mineral content (BMC) than white children. We examined the hypothesis that differences in insulin-like growth factors (IGFs) are important determinants of BMD during childhood.
We measured IGFs and IGF binding proteins in 59 African American and 59 white girls matched for age, body mass index, socioeconomic status, and pubertal stage. BMD and BMC were determined by dual emission x-ray absorptiometry.
African American girls had greater total BMD (P <.001), BMC (P <.01), total IGF-1 (P <.001), and free IGF-1 (P <.01) than white girls. IGFBP-1, IGFBP-2, and IGFBP-3 were similar in both groups or lower in African Americans. IGF-1 was positively correlated with IGF-2 in white girls (P =.012) but was negatively correlated with IGF-2 in African Americans (P =.015). IGF-1 and free IGF-1 were positively correlated with BMD/BMC. Multiple regression analyses showed 80% of the variance in BMC could be accounted for by the use of body weight, height, and IGF-1 in the model. When IGF-1 was included as a factor, race did not add to the model's predictive power.
IGF-1 and free IGF-1 are greater in African American than in white girls and may contribute to the greater BMD of African Americans.
Dietary soy protein compared with casein retards disease progression in a gender-specific manner in the pcy mouse. In this model of polycystic kidney disease (PKD), kidney insulin-like growth factor-I (IGF-I) levels are elevated. The present study examined the gender-specific effects of soy protein feeding on disease and IGF-I in Han:SPRD-cy rats.
Normal (+/+) and affected (cy/+) weanling male and female Han:SPRD-cy rats were given either casein- or soy protein-based diets for six weeks. Renal size, water content, cyst size and IGF-I, serum creatinine, urea and IGF-I, and creatinine clearance were determined.
Soy protein-fed cy/+ animals had lower kidney weight, water content and cyst size, lower serum urea and creatinine, and higher creatinine clearance. In cy/+ females, dietary soy protein resulted in normalized serum creatinine and creatinine clearance. Kidney IGF-I levels (ng/kidney) were 32 to 76% higher in cy/+ compared with +/+ groups (P < 0.001). Soy protein feeding resulted in lower kidney IGF-I in cy/+ males (1123 vs. 1496 ng/kidney, P < 0.001) and cy/+ females (816 vs. 943 ng/kidney, P < 0.05). In males, soy protein feeding resulted in lower serum IGF-I concentrations in +/+ (1439 vs. 1708 ng/mL, P < 0.05) and in cy/+ (1483 vs. 2073 ng/mL, P < 0.001) animals.
Dietary soy protein compared with casein delays the progression of disease in male and female Han:SPRD-cy rats. Overall, IGF-I was lower in +/+ animals, in females, and in animals consuming the soy protein diet, supporting a role for IGF-I in the pathogenesis of disease in the Han:SPRD-cy rat and an ameliorating role for dietary soy protein.
The objective was to assess effects of long-term treatment with recombinant bovine somatotropin (bST) and estradiol-17beta (E2) on the number of follicles that ovulated in response to FSH. Non-lactating Holstein and Jersey cows (Trial 1, n=27) and Angus cows and heifers (Trial 2, n=35) received two ear implants of E2 and biweekly injections of bST in a 2 x 2 arrangement of treatments. Estradiol implants were removed 74.6 +/- 1.1 d after insertion and 18.1 +/- 0.9 d after the last biweekly injection of bST. Cows were stimulated with FSH-P beginning 2 d after removal of E2 implants, and PGF2alpha (PGF) was given on the third day of FSH treatment. Ovaries were collected to determine the number of CL at 1 to 2 wk after treatment with PGF. In Trial 2 only, cattle were inseminated at estrus and embryos were collected 6 to 8 d later. Implants of E2 increased (P < 0.01) serum E2 8-fold initially and E2 was still elevated 5-fold at removal of implants. Injections of bST increased (P < 0.01) serum growth hormone (GH) 15-fold and insulin-like growth factor-I (IGF-I) 3-fold. In Trial 1, number of CL was increased by the combination of bST+E2 (P < 0.01). In Trial 2, E2 increased the number of CL (P < 0.05), and bST increased the number of total ova and transferable embryos (P < 0.01). We conclude that long-term treatment with bST and E2 may interact to enhance follicular development and ovulatory response to FSH.
Gonadotropins are well known to be the most important stimulus for ovarian follicular development. More recently, there is indirect evidence that insulin-like growth factor-1 (IGF-1) is also a very important autocrine/paracrine factor in folliculogenesis. We had access to an analog of IGF-1, LR3IGF-1, which binds very poorly to IGF-1 binding proteins and therefore was shown by previous investigators to have biologic effects. We studied rats that were superovulated with the use of gonadotropins. We showed that the addition of LR3IGF-1 by infusion further increased the ovulation rate (statistically significant) and increased the ovarian weight in two of three strains of rats. We demonstrated that infusion of LR3IGF-1 or injection of equine chorionic gonadotropin or a combination of these two were associated with oocytes with reduced number of cumulus cells (statistically significant). We conducted an experiment to determine whether in vitro culturing with varying dosage of IGF-1 may stimulate cumulus cell replication to improve the quality of oocyte cumulus complex. IGF-1 did not show any change in this respect. Through these physiologic (pharmacologic) studies, we have shown that IGF-1 (analog) can further increase the ovulation rate induced by gonadotropins.
Culture of preimplantation embryos is complex and requires strictly defined culture media to sustain their viability and quality. In the current study, an effort was made to evaluate comprehensively the quality of mice embryos, grown in media enriched with IGF I, IGF II, EGF and TNFalpha. For that purpose, critically chosen and thoroughly described, complex morphological methods based on contrast-phase, fluorescent and confocal microscopy were used. The study evaluated blastulation and hatching rates, total blastocyst cells, inner cell mass cell numbers (differential staining) as well as identified embryo cells with positive reactions for necrosis or apoptosis (TUNEL). The critical evaluation of the effects of the studied cytokines allowed for simultaneous, meticulous assessment of the applied study methods. Significantly more blastocysts were found in culture media enriched with IGF-I, IGF II and EGF. Significantly more hatched blastocysts were found in media with IGF-I and IGF II. Additionally, IGF I and II increased inner cell mass and total blastocyst cell numbers. Very few cells with necrosis and apoptosis were found in the culture media enriched with IGF I, IGF II and EGF. TNFalpha produced negative effects. The observed effects were dose-dependent.
To examine the possible role of calcium in conjoined twinning.
Conjoined (CJ) twins are an extreme example of monozygotic (MZ) twinning. Data were collected from various sources on factors to which gravidas who deliver CJ twins were exposed around the time of conception.
A significant number of such women were subjected to environmental triggers. Of particular interest is increased CJ twinning following use of oral contraceptives. It is hypothesized that this resulted from prolonged ovulatory dysfunction in lightweight women. The incidence of uniovular twinning is inversely related to women's prepregnancy weights.
These observations are consistent with the proposed general model of MZ twinning. Factors that induce calcium depression and delayed implantation encourage uniovular duplication in general and CJ twinning in particular.
Nutrition has long been known to have a profound influence on reproductive performance of female cattle, but the underlying mechanism remains poorly understood. Whilst early investigations focused on the modulation of nutrition on hypothalamic-pituitary axis, more recent studies have tested the hypothesis that metabolic hormones as nutritional signals exert a direct effect at the ovarian level. In cattle, treatment with recombinant bovine somatotrophin (rGH) significantly increases the population of small ovarian follicles. This is associated with increases in circulating concentrations of insulin and insulin-like growth factor-I (IGF-I). Subsequent studies, both in vitro and in vivo, have highlighted the importance of IGF-I and/or insulin acting in synergy with FSH and LH. More recently, we demonstrated that feeding heifers with 200% maintenance requirements for a short period significantly increases circulating insulin concentrations and population of small ovarian follicles. Based on these findings, our recent work has aimed at addressing some practical problems in cattle production. Firstly, we showed that both rGH pretreatment and increased dietary intake significantly enhance the response to standard superovulatory regimes. Secondly, we have demonstrated that feeding a diet to increase circulating insulin concentrations during the early lactation can advance the first ovulation postpartum and increase conception rate to the first service in dairy cows. In summary, nutrition influences ovarian follicle development in cattle possibly through changes in metabolic hormones. These interactions can be manipulated to improve reproductive performance.
To examine the possible role of inheritance in monozygotic twinning.
Via public announcement in national media, volunteers were requested who had given birth to monozygotic (MZ) twins or triplets and who also had relatives with twins. From the data received, common factors in such sets were sought. Zygosity was confirmed with various combinations of placental pathology, sex, blood type, DNA analysis, fingerprints and physical appearance.
Among the 109 responses, 78 mothers of MZ multifetal pregnancies with twin relatives were identified. Of special interest were 13 cases of triplets that resulted from transfer of 2 viable embryos during in vitro fertilization (IVF). Each of these cohorts had twin relatives. They were compared to 33 cases of spontaneous MZ triplets, also with twin relatives. The familial clustering phenomenon appeared to be a function of maternal age, whereas the effect of zygosity or lineage (paternal versus maternal) of the related twins was nonspecific.
The findings are consistent with the suggested influence of genetics and familial clustering on the MZ twinning rate, especially in IVF procedures. The risk of unintended dizygotic triplet pregnancies could be reduced by limiting transfer to 1 embryo in cases of older women with a family history of multiple gestation. Roles of calcium and insulinlike growth factor in this phenomenon appear plausible.
The dizygotic twinning rate fell during the war in France, Holland, and Norway, but not in Denmark, Sweden, or the North-West of France ; the monozygotic twinning rate remained constant in all these countries. It is suggested that this was due to a decreased tendency of the ovary to produce double ovulations, which was caused by undernutrition. © 1959, British Medical Journal Publishing Group. All rights reserved.
Data are presented on the twinning rate among Europeans and Negroes. The monozygotic twinning rate is constant; there is, however, considerable variation in the dizygotic rate. The dizygotic rate is higher among Negroes than Europeans. There are also variations within these groups. In particular there seems to be a centre of low twinning rate in south-west Europe.
I should like to thank the following who have gone to great trouble in sending me data: E. A. Barker, Nqutu, Zululand; C. J. Dricot, Leopoldville; S. H. O. Jones, Bathurst, Gambia; Yayoichi Karube, Tokyo; Prof. Lambillon, Leopoldville; J. B. Lawson, Ibadan, Nigeria; J. M. Samson, Johannesburg; Prof. J. B. Stewart, Jamaica; K. H. Uttley, Antigua.