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Early nutritional programming and progeny performance: Is reproductive success already set at birth?

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Implications • Maternal nutrition during gestation influences the development and function of many biological systems in offspring. • There is evidence to show that both maternal undernutrition and overnutrition during gestation are detrimental to the reproductive development of offspring and that the effects are permanent after birth and visible in adulthood. • These long-term effects may impair reproductive efficiency in the offspring; hence, nutrition during the entire gestation should be carefully managed to improve fertility.
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Key words: development, gonads, nutrition, offspring, reproduction
Introduction
Compelling evidence indicates that the environment encountered dur-
ing fetal life exerts a profound inuence on development, physiological
function, and risk of disease in adult mammals (Barker, 2007; Langley-
Evans and McMullen, 2010). Development is a plastic process, wherein a
range of different phenotypes can be expressed from a given genotype. The
developing conceptuses respond to conditions in the environment during
sensitive periods of cellular proliferation, differentiation, and maturation,
resulting in structural and functional changes in cells, tissues, and organ
systems. These changes may have short- and/or long-term consequences
for health and disease susceptibility. Hence, the term “programming” has
been adopted to describe the process whereby a stimulus or an insult at a
critical and sensitive period of fetal or perinatal life has permanent effects
on the structure, physiology, and metabolism of different organs and sys-
tems. Despite many studies investigating the associations between mater-
nal environment during fetal development and the onset of cardiovascular
disease, obesity, and diabetes in offspring as adults (McMillen and Robin-
son, 2005), few studies have investigated the impact of maternal environ-
ment on the reproductive potential of offspring. This paper reviews the
existing literature on the effects of prenatal and perinatal nutrition on the
development and function of the reproductive system in female and male
domestic mammals, with particular emphasis on cattle and sheep.
Development of the Reproductive
Tract in Female and Male Mammals
In mammals, sex is genetically determined, whereby embryos with an
X and a Y chromosome develop as males and those with two X chro-
mosomes develop into females. Nevertheless, during the initial stages of
gonadal and genital development, embryos of either sex are morphologi-
cally indistinguishable. The urogenital system comprises the gonads, kid-
neys, urinary, and reproductive tracts and develops from the intermedi-
ate mesoderm, formed during gastrulation of the embryo. Before sexual
differentiation, the intermediate mesoderm proliferates and generates two
pairs of genital ducts: the Wolfan (or mesonephric) and the Müllerian (or
paramesonephric) ducts. Sexual differentiation in males is characterized
by regression of the Müllerian ducts due to the inhibitory effect of anti-
Müllerian hormone (AMH), which is secreted by the Sertoli cells of the
fetal testis, thus enabling differentiation of the Wolfan ducts into struc-
tures of the male reproductive tract, such as the epididymides, vas def-
erentia, and seminal vesicles. Fetal ovaries do not produce AMH, so the
Müllerian ducts that subsequently form adjacent to the Wolfan ducts can
persist and differentiate into the oviducts, uterus, cervix, and upper por-
tion of the vagina of the female reproductive tract (Spencer et al., 2012).
Early nutritional programming and
progeny performance: Is reproductive
success already set at birth?
Francesca Mossa,* Siobhan W. Walsh,† James J. Ireland,§ and Alexander C.O. Evans¶
* Department of Veterinary Medicine, University of Sassari, Italy
† Department of Chemical and Life Sciences, Waterford Institute of Technology, Ireland
§ Department of Animal Science, Michigan State University, East Lansing, Michigan, USA;
¶ School of Agriculture and Food Science, University College Dublin, Ireland
Implications
Maternal nutrition during gestation inuences the development
and function of many biological systems in offspring.
There is evidence to show that both maternal undernutrition and
overnutrition during gestation are detrimental to the reproductive
development of offspring and that the effects are permanent after
birth and visible in adulthood.
These long-term effects may impair reproductive efciency in the
offspring; hence, nutrition during the entire gestation should be
carefully managed to improve fertility.
© Mossa, Walsh, Ireland, and Evans.
doi:10.2527/af.2015-0004 Newborn calf overies and uterus.
18 Animal Frontiers
The source and migration of germ cells to the developing gonads is the
same in males and females. When primordial gonads begin to differentiate
as ovaries or testes, developmental pathways of germ cells diverge, leading
to either oogenesis in females or spermatogenesis in males. In a newly spec-
ied ovary, germ cells enter into the rst phase of meiosis—the special form
of cell division unique to germ cells that allows them to produce haploid
cells necessary for sexual reproduction. In the fetal ovary, entry into meiosis
is seen as the rst indication that germ cells have embarked on oogenesis.
In a newly specied testis, germ cells enter a period of mitotic quiescence
and remain in that state until just before puberty when meiosis commences
(Spiller et al., 2012). The timing of development of the reproductive tract
differs among species and between sexes; hence, the effect of a nutritional
insult may vary depending on the species, the timing at which it occurs, and
on fetal gender. Table 1 summarizes the current knowledge for laboratory
rodents, sheep, cattle, and humans. Gestation has been divided into three
parts to better emphasize how the development of the reproductive system
may be differentially sensitive during selected windows of gestation.
Early Maternal Nutrition and Female Offspring
Reproductive Development and Function
The effect of a specic environment in utero on the development of the
conceptus may be different for female and male offspring. Table 2 sum-
marizes the effects of nutritional manipulation of dams during gestation
and lactation on reproductive development in female offspring.
Undernutrition
Farm animals may often be exposed to nutritional deciencies during
gestation and lactation; small ruminants are commonly farmed in areas of
marginal land on which nutrient supply may be scarce, and dairy cattle may
experience periods of negative energy balance at the start and peak of their
lactation, which coincides with the time of insemination and early gestation.
Hence, efforts have been aimed at understanding the link between undernutri-
tion and reproductive performance for both research and production scopes.
Sheep. The effect of maternal undernutrition on fetal ovarian develop-
ment was rst investigated in ewes fed either 150% (High Energy) or 50%
(Low Energy) of their energy requirements for maintenance (M) during
early gestation (Borwick et al., 1997). At Day 47 (rst third) of gestation,
concentrations of oogonia were greater in ovaries of Low compared with
High Energy fetuses. At Day 62 (rst and start of second third) of gesta-
tion, the process of germ cell degeneration was less advanced in Low than
High Energy fetal ovaries, as indicated by greater oocyte concentrations
and a greater percentage of meiotic cells in Low vs. High Energy ovaries.
The authors concluded that undernutrition from the time of mating retards
ovarian development in fetal ovaries (Borwick et al., 1997). Nevertheless,
Table 1. Timing of reproductive tract development in laboratory rodents, sheep, cattle, and humans. Gestation
has been divided into three parts to better emphasize how the development of the reproductive system may be
differentially sensitive during selected windows of gestation (Rüsse, 1983; Dupont et al., 2012; Spencer et al., 2012).
Event (day of gestation/day after birth)
Rodents* Sheep Cattle Humans
1st third of
gestation
gonadal differentiation (mice 6) Müllerian ducts formed (24) germ cells visible (35-36) male gonadal differentiation (42-49)
germ cells visible (6.5) male gonadal differentiation (30) start of meiosis in female (75-80) Müllerian ducts fusion (by 56)
Müllerian ducts fusion (34-55) primordial follicles
visible in female
(74-90)
start of meiosis in female (70-98)
start of meiosis in female
(55)
uterine corpus and cervix
differentiated (by 84)
2nd third of gestation
germ cells migrate towards
the genital ridges (8.5-10.5)
primordial follicles visible in female
(75)
primary follicles visible in female
(74-140)
primordial follicles visible in female
(98-105)
Wolfan ducts formed (9) aglandular nodules visible
in the uterine endometrium (90)
peak number of germ cells
(91-110)
tertiary follicles visible
(210-245)
Müllerian ducts formed (11.5) primary follicles visible in female
(110)
secondary follicles visible
(120-210)
gonadal differentiation (rat 12.5)
start of meiosis in female
(mice 13, rat 17)
regression of Müllerian ducts in male
(13.5)
3rd third of
gestation
fusion of Müllerian ducts
(15-16)
endometrial gland development
rst observed (135)
antral follicles visible
(135)
Birth 20 mice, 21 rat 147 282 280
Postnatal life
meiosis of germ cells in male development of the uterus (up to 26) Development of endometrial glands
(birth-puberty)
development of the uterus (1-15)
primordial follicles
(mice 2-5, rat 1-2)
primary follicles (mice 2-5, rat 2-3)
antral follicles (mice 17, rat 15)
*Data for rodents are expressed as days post-coitum.
Jan. 2015, Vol. 4, No. 1 19
it must be noted that this study compared a Low vs. High Energy diet, but
no comparisons were made with a moderate energy diet.
Another trial conducted in ewes reported a delay in fetal ovarian fol-
licular development at Day 110 of gestation as a result of undernutrition
(50% M) vs. control diet (100% M) during different periods of pregnancy
(Rae et al., 2001), conrming the negative effect of maternal undernutri-
tion on fetal ovarian development. It is noteworthy that ovaries were not
examined after birth; hence, a compensatory effect during the remainder
of gestation cannot be excluded. Nevertheless, a similar nding was re-
cently reported in prepubertal lambs; maternal nutritional restriction from
mating to Day 7 or Day 15 (rst third) of gestation resulted in an increase
in the total population of oocytes in one- and two-month-old ewe-lambs,
respectively (Abecia et al., 2014a, 2014b). We can thus speculate that an
increase in the number of oogonia in fetal and prepubertal ovaries exposed
to maternal undernutrition may reect a delay in ovarian development in
sheep, but whether this delay has long-term effects on reproductive ef-
ciency after puberty is still unknown.
A study that examined the link between in utero malnutrition and repro-
ductive efciency in ovine adult offspring reported reduced ovulation rates
in adult offspring of undernourished mothers from mating until Day 95 (rst
and second third) of gestation compared with controls (Rae et al., 2002a).
It appears that an increase in the number of oocytes assessed during fetal/
prepubertal life may not reect better reproductive performance after puberty
in sheep. Interestingly, a cohort of ewes born to mothers undernourished dur-
ing the last 100 days (second and third third) of pregnancy did not present an
impairment in ovulation rate (Gunn et al., 1995); this is probably due to the
fact that undernutrition was imposed during a late window of development.
Ten-month-old female lambs undernourished as fetuses during the rst month
(rst and start of second third) of pregnancy had a greater FSH response to
GnRH challenge and greater number of small (2 to 3 mm diameter) follicles,
whereas when nutritional restriction was imposed from Day 31 to 100 (start
of rst and second third) of gestation, fewer corpora lutea were observed,
indicating a decreased number of ovulations (Kotsampasi et al., 2009b).
Taken together, these studies provide evidence that in utero undernutri-
tion of female ovine fetuses during the rst and second third of gestation:
1) causes an increase in the number of oogonia in fetal and prepubertal
ovaries, which is likely to reect a delay in ovarian development; and 2)
reduces ovulation rate in adulthood. These results support the hypothesis
of a negative effect of undernutrition during early- and mid-pregnancy on
female reproductive development in sheep.
Nevertheless, the long-term impact of maternal undernutrition on re-
productive efciency in female offspring in sheep is yet to be completely
explored. The slow progress in this area is partly due to the fact that inves-
tigating how reproductive success can be programmed in utero/perinatally
in domestic animals is challenging because long trials are necessary to
allow the offspring to reach puberty and large numbers of animals are
required to conduct statistically valid studies.
Finally, the mechanisms whereby undernutrition may alter follicular de-
velopment in utero, and consequently reproductive efciency after birth, are
still unclear. Underfeeding from 65 to 110 d (second third) or from 0 to 110 d
Table 2. Effects of nutritional manipulation of dams during gestation and lactation on reproductive development in
female offspring.
Species Maternal diet Period of diet Effect on the offspring Reference
1st third of gestation
Sheep Undernutrition Mating to early gestation Delayed fetal ovarian development
at 47 and 62 d of gestation
(Borwick et al., 1997)
Sheep Undernutrition Mating to 7 d Mating to15 d Increased total number
of oocytes at 1 and 2 mo old
(Abecia et al., 2014a;
Abecia et al., 2014b)
Sheep Undernutrition Mating to 30 d Increased FSH response to GnRH
and small follicles at 10 mo old
(Kotsampasi et al., 2009b)
Sheep Undernutrition 31 to 100 d Decreased number
of corpora lutea at 10 mo old
(Kotsampasi et al., 2009b)
Cattle Undernutrition -11 d before insemination – 110 d Decreased number of follicles,
lower AMH and higher FSH concentrations
(Mossa et al., 2013)
Cattle Low-high protein Low protein in rst trimester,
high protein in second trimester
Smaller largest follicle before
puberty, lower densities of primordial,
primary and healthy antral follicles as adults
(Sullivan et al., 2009)
2nd and 1st-2nd
third of gestation
Sheep Undernutrition Various periods mating to 110d Delayed fetal ovarian
development at 110 d gestation
(Rae et al., 2001)
Sheep Undernutrition 65 to110 d; 0 to 110 d Alteration of the expression
of genes that regulate apoptosis
(Lea et al., 2006)
Sheep Undernutrition Mating to 95 d Reduced ovulation rate in adults (Rae et al., 2002a)
Sheep Overnutrition Mating to 130 d; 4 to 130 d Fewer follicles in fetuses (Da Silva et al., 2002, 2003)
3rd third and entire gestation
Cattle Overnutrition Third trimester Higher proportion of heifers calved
in the rst 21 d of their rst calving season
(Cushman et al., 2014)
Sheep Undernutrition 47 to 147 d No difference in ovulation rate in adults (Gunn et al., 1995)
Rats Undernutrition Entire pregnancy and/or lactation Advanced pubertal age (Sloboda et al., 2009)
Rats High fat diet Entire pregnancy and/or lactation Advanced pubertal age (Sloboda et al., 2009)
Pig Low protein Entire pregnancy and lactation Reduced number of antral follicles,
increased apoptosis of granulosa cells, higher
estradiol concentrations in prepubertal offspring
(Sui et al., 2014)
Rabbit High fat From mating to 27 weeks of age Higher number of atretic follicles in adults (Léveillé et al., 2014)
20 Animal Frontiers
(rst and second third) of gestation in sheep altered the expression of genes
that regulate apoptosis (Lea et al., 2006), but further studies are needed.
Cattle. To identify markers of reproductive potential, a series of ex-
periments conducted in our laboratories identied the number of antral
follicles growing during follicular waves (antral follicle count, or AFC)
and serum AMH concentrations as diagnostic markers for fertility in cattle.
Antral follicle count is positively associated with the number of morpho-
logically healthy follicles and oocytes in ovaries (ovarian reserve; Ireland
et al., 2008), and cattle with a low AFC have a reduced response to su-
perovulation (Ireland et al., 2007), enhanced FSH secretion (Burns et al.,
2005), decreased progesterone production, and reduced endometrial thick-
ness from Day 0 to 6 of the estrous cycle compared with age-matched
cattle with high AFC (Jimenez-Krassel et al., 2009; Ireland et al., 2011). In
addition, dairy cattle with ≤ 15 ovarian follicles have a reduced reproduc-
tive performance compared with cows with greater numbers of follicles
(Mossa et al., 2012). Based on these results, we used AFC, AMH, and FSH
as markers of the size of the ovarian reserve and reproductive potential
to investigate the effect of maternal nutritional restriction during the rst
trimester of pregnancy on development of female offspring. Female calves
born to nutritionally restricted mothers (0.6M for the rst 110 d of gesta-
tion; rst third of gestation) showed lower AFC, lower AMH, and greater
FSH concentrations but had similar birth weights, postnatal growth rates
(to 95 wk of age), age at puberty, glucose metabolism, and responses to
stress compared with offspring from control mothers (1.2M; Mossa et al.,
2013). Interestingly, female calves born to nutritionally restricted mothers
also had an enlarged aorta and increased arterial blood pressure compared
with controls. Whether such phenotypes were both direct consequences of
maternal undernutrition or whether compromised vascular function dimin-
ished the ovarian reserve and potential fertility is unknown. This study pro-
vides evidence for a negative impact of maternal malnutrition on reproduc-
tive capacity in adult offspring, but it did not investigate the mechanisms
that mediated the effect of maternal undernutrition on ovarian reserve in
the offspring. However, an increase in maternal testosterone concentration
was detected during dietary restriction in our study.
Another study conducted in cattle provides evidence of the negative
effect of early undernutrition on female gonadal development. Heifers
born to dams that received a low-protein diet during the rst trimester fol-
lowed by a high-protein diet during the second trimester of pregnancy had
smaller follicles and fewer primordial and primary follicles and healthy
antral follicles as adults (Sullivan et al., 2009).
Studies investigating maternal undernutrition and offspring reproduction
in cattle are limited, probably because of the high costs of such trials due to
the length of pregnancy in this species. Findings presented here show that
maternal undernutrition during the rst third of gestation is inversely associ-
ated with several markers of reproductive efciency in female offspring.
Pigs and rodents. A low-protein diet during gestation and lactation
in sows caused a reduction in the number of antral follicles, coupled with
an increase in apoptotic granulosa cells and greater circulating estradiol
concentrations in prepubertal offspring (Sui et al., 2014). Similarly, in
rats, maternal protein restriction decreased numbers of preantral and an-
tral follicles and altered the expression of key genes involved in follicular
development and steroidogenesis (Guzmán et al., 2014). The reduction in
number of follicles observed in offspring of undernourished mothers after
birth appears to be coupled with an alteration in follicular atresia (apopto-
sis) and steroidogenic activity. Also, in rats, maternal nutrient restriction
during pregnancy and/or lactation signicantly advanced pubertal age in
female offspring (Sloboda et al., 2009).
Hence, the aforementioned negative association between maternal un-
dernutrition and offspring reproductive efciency observed in sheep and
cattle is conrmed in pigs and rats, despite the difference in placentation
and in the number of fetuses per pregnancy among these species.
Overnutrition
The study of overnutrition in domestic animals has recently received
considerable attention, particularly as a model for humans because obesity
has become a global epidemic and diets with high concentrations of fat or
sugar are unfortunately common in pregnant women. Yet the number of
studies investigating the possible link between maternal overnutrition and
fertility in the offspring is limited.
Sheep. A study in sheep reported fewer follicles in the ovaries of fe-
male fetuses exposed to high compared with moderate levels of a complete
diet from Day 4 to 130 (Da Silva et al., 2002) or from mating to Day 130
of gestation (Da Silva et al., 2003). These studies show that overnutrition,
similarly to undernutrition, in early- to mid-gestation may impair the es-
tablishment of the ovarian follicular reserve and consequently reproductive
potential in female fetuses. Nevertheless, it must be noted that fetal ovaries
were examined and further research is needed to determine the long-term
effects in ovaries of adult ewes exposed to overnutrition as fetuses.
Cattle. In cattle, a recent study reported that increasing maternal di-
etary intake during late gestation had no effect on age at puberty or AFC in
Jan. 2015, Vol. 4, No. 1 21
female offspring, but an increased proportion of the heifers born to dams
fed a high-nutrient diet during the third trimester calved in the rst 21 d of
their rst calving season (Cushman et al., 2014). In turn, AFC was greater
in heifers that calved during the rst 21 d of their rst calving season, thus
conrming the usefulness of AFC as a predictor of reproductive capacity
(Cushman et al., 2014).
This study provides evidence for a moderate positive effect of a diet
with high nutritional levels during the last third of gestation on reproduc-
tive efciency in female offspring. It is noteworthy that the development
of the ovarian reserve and age at puberty were not affected by maternal
diet, probably because differential diets were imposed during late gesta-
tion, when follicles are already formed.
Rabbits and rodents. Sexually mature rabbits exposed to a high-fat
diet as fetuses and from birth to 27 wk of age had greater numbers of
atretic follicles but similar numbers of primordial, primary, and secondary
follicles compared with controls, and their reproductive capacity was not
altered (Léveillé et al., 2014). In rats, maternal consumption of a high-fat
diet both before and during pregnancy and lactation, or only during preg-
nancy and lactation, signicantly advanced the age of puberty and caused
obesity in female offspring (Sloboda et al., 2009).
Taken together, these results provide evidence for a negative effect of
overnutrition on fetal ovarian development and age at sexual maturation,
but long-term studies are needed to conrm an impairment of reproduc-
tive capacity in adulthood.
Early Nutrition and Male
Reproductive Development and Function
Undernutrition
Table 3 summarizes the studies reporting effects of nutritional manipu-
lation of dams during gestation and lactation on reproductive develop-
ment in male offspring.
Sheep. As described earlier, maternal undernutrition during early gesta-
tion in sheep altered fetal ovarian development (Rae et al., 2001; Lea et al.,
2006), but the same diet during the same period (from mating to Day 110;
rst and second third of gestation) had no effect on number of Sertoli cells
nor on expression of gene products that regulate apoptosis in male offspring
(Andrade et al., 2013). Nonetheless, maternal undernutrition applied from
mating to Day 50 (rst third) of gestation resulted in an increased expression
of mRNA for steroidogenic acute regulatory protein (StAR) in fetal testes,
a protein involved in transport of cholesterol to mitochondria for steroido-
genesis, indicating a possible upregulation of fetal testicular steroidogenesis
(Rae et al., 2002b). Furthermore, male lambs exposed to undernutrition from
31 to 100 d (end of rst and second third) of gestation had an increased FSH
response to a GnRH challenge coupled with fewer Sertoli cells at 10 mo of
age (Kotsampasi et al., 2009a). Finally, a study in sheep where maternal un-
dernutrition was imposed from 10 wk of gestation until parturition (second
and third third of gestation) produced male offspring with fewer Sertoli cells
and smaller volumes of testicular cords at birth (Alejandro et al., 2002)..
Rodents. In rats, maternal protein restriction during pregnancy and/or
lactation caused a reduction in LH and testosterone concentrations at 70 d
of age in male offspring as well as reduced fertility rates and sperm counts
at 270 d of age (Zambrano et al., 2005).
Findings in both sheep and rats indicate that undernutrition during
pregnancy can reduce testicular development in the newborn, as assessed
by a reduction in the number of Sertoli cells.
Overnutrition
In humans, obesity is often caused by excessive consumption of high
energy (usually high in sugar and/or fat).
Rodents and rabbit. To investigate the potential effects of such diet
on health, researchers conduct experiments on laboratory rodents using the
“cafeteria diet,” which is composed of highly energetic and palatable human
foods (Jacobs et al., 2014). The cafeteria diet includes biscuits, ham, cake,
marshmallows, sausages, salami, and soft drinks. The majority of studies
focus on metabolic syndrome, obesity, and cardiovascular disease. Yet, in a
recent work, adult male offspring of female rats fed a cafeteria diet before
gestation (from 21 d of age to mating at 90 d), during gestation and lactation,
or from before gestation to lactation showed impaired reproductive behavior,
as assessed by a reduction in the percentage of animals displaying intromis-
sion behavior and decreases in plasma concentration of testosterone, LH,
and FSH (Jacobs et al., 2014). Also, rabbits fed a dietary-induced maternal
hyperlipidemia and hypercholesterolemia, administered from 10 wk of age
and throughout gestation and lactation, had male offspring with lighter testes
Table 3. Effects of nutritional manipulation of dams during gestation and lactation on reproductive development in
male offspring.
Species Maternal diet Period of diet Effect on the offspring Reference
1st third
of
gestation
Sheep Undernutrition Mating to 50d Increased expression
of mRNA for steroidogenic
acute regulatory protein (StAR)
(Rae et al., 2002b)
2nd third
of
gestation
Sheep Undernutrition 31 to 110 d Increased FSH response to GnRH
challenge, fewer Sertoli cells at 10 months of age
(Kotsampasi et al., 2009a)
Cattle Low protein
and low energy diet
1st and 2nd
trimester
Increased FSH concentration
and increased testicular volume at 5 months of age
(Sullivan et al., 2010)
3rd third
of gestation
and entire gestation
Sheep Undernutrition 110 d
to lambing
Fewer Sertoli cells and smaller
volume of testicular cords at birth
(Alejandro et al., 2002)
Rat Low protein Pregnancy and/or lactation Reduced LH and testosterone concentrations at 70d of age;
reduced fertility rate and sperm count at 270d of age
(Zambrano et al., 2005)
Rat Cafeteria diet Before gestation -
weaning; mating-weaning
Impaired sexual behavior, lower
FSH, LH, and testosterone concentrations as adults
(Jacobs et al., 2014)
Rabbit Hyper-lipidic
hyper-cholesterolemic diet
Before
gestation - weaning
Lighter testes and epididymis
and decreased testosterone concentrations as adults
(Dupont et al., 2014)
22 Animal Frontiers
and epididymis and decreased testosterone concentrations compared with off-
spring born to control dams as adults (Dupont et al., 2014).
Cattle. Prepubertal bull calves whose mothers were fed a diet low in pro-
tein and energy levels during the rst and second trimester of pregnancy had
increased prepubertal FSH concentrations and testicular volume compared
with calves born to mothers fed a high-protein diet, suggesting a deleterious
effect of elevated dietary protein and energy in the rst trimester of gestation
on reproductive development of their bull calves (Sullivan et al., 2010).
These studies, although limited in number, suggest that male offspring
of overnourished mothers may have compromised reproductive potential.
Conclusions
The impact of maternal nutritional imbalance on the development and fu-
ture function into adulthood of the reproductive systems in both their female
and male offspring is relevant. The timing at which mothers are exposed to
under- or overnutrition is as signicant as the severity of the nutritional imbal-
ance, but many questions remain to be answered. These include whether in
utero nutritional effects on reproductive development and function are perma-
nent or reversible. Could heifers exposed during early uterine life to malnutri-
tion, due to, for example, a particularly dry season, be “treated” with a specic
compensatory diet later in gestation or early postnatally?
Mechanistic studies are also needed to clarify the paths through which
an improper diet affects the growth and function of the reproductive or-
gans and if other factors, such as heat stress during gestation, inuence
reproductive development and function in offspring.
The real challenge for future studies is to understand how the prenatal
environment can be managed to improve reproductive performances of
farm animals. As such, more research efforts are needed to understand the
extent and the mechanisms whereby maternal nutrition programs repro-
ductive success of their offspring.
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Francesca Mossa is a senior researcher within
the Department of Veterinary Medicine at the
University of Sassari (Università degli Studi
di Sassari, Uniss), Italy. She graduated with
a Doctor in Veterinary Medicine (DVM) and
received her Ph.D. at Uniss. She subsequently
worked as a post-doctoral research scientist
at University College Dublin, Ireland. She
lectured in animal reproduction at Uniss
and worked as a manager on a dairy sheep
farm. She returned to research when she was
awarded the “Rita Levi Montalcini Program
for Young Researchers.” Her research focuses
on ovarian development and developmental programming of reproduction.
Correspondence: fmossa@uniss.it
Siobhán Walsh is currently an agricultural
science lecturer within the Department. of
Chemical and Life Sciences at Waterford
Institute of Technology, Ireland. Having
completed a BAgrSc in animal science from
University College Dublin (UCD), Ireland,
Siobhán undertook a research masters where
her research focused on the effects of breed
and feeding system on milk production, udder
health, and fertility performance across two
grass-based feeding systems in Ireland. Fol-
lowing the MAgrSc, she pursued a Ph.D. in
the School of Agriculture and Food Science at
UCD investigating factors that affect ovarian follicle development. Specically,
her research focus is the role of ovarian follicles in successful reproduction us-
ing different animal models.
James J. Ireland is Professor in the Ani-
mal Science and Physiology Departments
at Michigan State University. His research
program focuses on the role of the inherently
high variation in follicle and oocyte num-
bers in ovaries on ovarian function, oocyte
and embryo quality, fertility, and health in
cattle and has been funded nearly continu-
ously since 1979 by grants from USDA, NSF,
NIH, industry, and the Michigan Agricultural
Experimental Station. His research has been
published in numerous scientic refereed
journals, and he has provided leadership to
explain why enhanced federal funding for farm animal research in the U.S. is
critical to animal agriculture and human health.
Professor Alexander Evans is the Dean of
Agriculture and Head of the School of Ag-
riculture and Food Science at the Univer-
sity College Dublin, Ireland. He has a B.Sc.
in animal Science (Nottingham University,
UK), a Ph.D. (University of Saskatchewan,
Canada), and a D.Sc. (National University of
Ireland). He has conducted research on a wide
range of topics focusing on reproduction with
a particular emphasis on the establishment of
pregnancy in cattle and sheep. Professor Ev-
ans has attracted more than €13 million of
research funding, has supervised more than
30 graduate students, has published more than 130 peer-reviewed papers, and is
the co-editor-in-chief of the international journal Animal Reproduction Science.
About the Authors
24 Animal Frontiers
... Additionally, poor maternal nutrition during gestation may be detrimental to reproductive performance in the offspring, as the development of the reproductive system is also affected. 6 Reproductive performance, particularly in males, is of great interest to the livestock industry, as an elite sire has a greater chance for breeding and reproducing a significant number of progeny. At present, virtually all bulls used for semen collection and AI are the result of embryo transfer (ET) from elite females. ...
... The specificity of the PCR product was confirmed by the melting curve and product size following electrophoresis in 2% agarose gel. Samples 1,2,3,4,5,6,9,and 11 were positive, whereas the bands in the other samples correspond to unspecified products. +: Positive control. ...
... Section 1. The Society shall further the science of embryo production, development, and transfer by (1) promoting more effective research; (2) disseminating scientific and educational information; (3) fostering high standards of education; (4) maintaining high standards of ethics; (5) enhancing the international movement of animal genetics with embryos; (6) coordinating standardization of embryo handling and record procedures internationally; and (7) cooperating with other organizations having similar objectives. ...
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This work aims to evaluate the efficiency of detecting embryonic DNA in extracellular vesicles (EVs) secreted by in vitro produced bovine embryos. It is hypothesized that embryonic DNA is released within EVs, and thus, the isolation of these vesicles would improve the use of spent medium as a noninvasive method for embryo sexing and genotyping. The presence of DNA was determined by the detection of gene fragments using PCR.
... This process is named 'programming'. Interest is growing on the potential for programming of the reproductive system in mammals (reviewed by Sloboda et al. 2011, Evans et al. 2012, Mossa et al. 2015), albeit studies investigating programming of the size of the ovarian reserve, and correspondingly of AMH production, in cattle are scarce. Maternal nutritional status is considered a major cause of fetal developmental programming in humans, cattle and sheep ( Gluckman & Hanson 2004, McMillen et al. 2008, El Hajj et al. 2014, Mossa et al. 2015). ...
... Interest is growing on the potential for programming of the reproductive system in mammals (reviewed by Sloboda et al. 2011, Evans et al. 2012, Mossa et al. 2015), albeit studies investigating programming of the size of the ovarian reserve, and correspondingly of AMH production, in cattle are scarce. Maternal nutritional status is considered a major cause of fetal developmental programming in humans, cattle and sheep ( Gluckman & Hanson 2004, McMillen et al. 2008, El Hajj et al. 2014, Mossa et al. 2015). We tested the hypothesis in cattle that dietary nutritional restriction (to 60% of maternal requirements) has permanent effects on the establishment of the ovarian reserve (total number of morphologically healthy follicles and oocytes) in offspring. ...
... Furthermore, infectious diseases and endocrine disorders are also noted to affect AMH synthesis by affecting the ovarian reserve. (Mossa et al., 2015;Mossa et al., 2017). Indeed, it was reported that ovarian reserve in pregnant cattle is negatively affected by nutritional deficiency (Mossa et al., 2010;Mossa et al., 2013). ...
... Nevertheless, what determines the size of the ovarian reserve in cattle is unclear. While recent studies report that AFC and AMH are moderately heritable traits in dairy cattle (Walsh et al., 2014;Nawaz et al., 2018;Gobikrushanth et al., 2019), evidence also indicates that the ovarian reserve might be influenced by the environment encountered during fetal life (Sloboda et al., 2011;Evans et al., 2012;Mossa et al., 2015;. Growing evidence indicates that a ruminant's maternal nutritional status can influence the development of the reproductive system in female (Borwick et al., 1997;Rae et al., 2001;Sullivan et al., 2009a,b;Mossa et al., 2013;Weller et al., 2016;Smith et al., 2019) and male offspring (Alejandro et al., 2002;Kotsampasi et al., 2009;Mossa et al., 2018). ...
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The objectives of this study were to establish if exposure of pregnant dairy cows to high environmental temperatures and humidity during the first trimester of pregnancy impairs the establishment of the ovarian reserve (total number of healthy follicles and oocytes in ovaries) and fertility in their offspring. Serum anti-Müllerian hormone (AMH) concentrations and number of follicles ≥3 mm (antral follicle count; AFC) were assessed on a random day of the estrous cycle in 310 sixteen-month-old dairy heifers. Based on season of their conception and early fetal life, heifers were separated into 2 groups: summer (mean monthly temperature-humidity index = 69.33 ± 2.6) and winter (temperature-humidity index = 54.91 ± 1.08). The AMH and AFC were lower in summer (419.27 ± 22.81 pg/mL and 9.32 ± 0.42 follicles, respectively) compared with winter heifers (634.91 ± 47.60 pg/mL and 11.84 ± 0.46 follicles, respectively) and were not influenced by farm and age at sampling. Heifers born to dams that were not being milked during gestation had lower AMH and AFC compared with offspring of cows on their first lactation, whereas no difference was detected between offspring of cows on their first and subsequent lactations. Summer and winter heifers had similar age at first service and at first calving, and similar number of services per conception. Regardless of season in early fetal life, heifers were classified into 3 groups based on AMH and AFC (low = 20%, intermediate = 60%, high = 20%). Heifers with the lowest AMH were older at first service compared with herd mates with intermediate AMH, but age at first calving and number of services per conception were similar among AMH categories. No difference was detected in any of the fertility measures among AFC categories. Heifers born to mothers exposed to high environmental temperatures in early gestation had smaller ovarian reserves compared with herd mates conceived in winter, but no association between season of early fetal life and fertility at first conception was established. Season of conception and maternal lacta-tion status affect the size of the ovarian reserve, but not fertility, at first conception in the progeny.
... Subsequent effects upon productivity include altered postnatal growth (Micke et al. 2010a) and reproductive development (Sullivan et al. 2009a;Mossa et al. 2013). However, it is acknowledged that the effects of maternal nutrition during the periconception period and early gestation on fetoplacental development in cattle are poorly understood (Mossa et al. 2015;Sinclair et al. 2016). ...
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Full-text available
Few studies have investigated the effects of nutrition during the periconception and early gestation periods on fetal and placental development in cattle. In this study, nulliparous yearling heifers (n=360) were individually fed a diet high or low in protein (HPeri and LPeri) beginning 60 days before conception. From 24 to 98 days after conception, half of each treatment group was changed to the alternative high- or low-protein diet (HPost and LPost) yielding four groups in a 2×2 factorial design. A subset of heifers (n=46) was necropsied at 98 days after conception and fetoplacental development assessed. Placentome number and volume decreased in response to LPeri and LPost diets respectively. Absolute lung, pancreas, septum and ventricle weights decreased in LPost versus HPost fetuses, whereas the post-conception diet altered absolute and relative liver and brain weights depending on sex. Similarly, changes in fetal hepatic gene expression of factors regulating growth, glucose output and lipid metabolism were induced by protein restriction in a sex-specific manner. At term, neonatal calf and placental measures were not different. Protein restriction of heifers during the periconception and early gestation periods alters fetoplacental development and hepatic gene expression. These changes may contribute to functional consequences for progeny, but this may not be apparent from gross morphometry at birth.
... Under adverse intrauterine conditions, the fetus could permanently modify some endocrine functions to ensure its survival [6]. The structure, physiology and metabolism of different organs and systems could be modified, leading to detrimental postnatal metabolic changes [7] and predisposing offspring to cardiovascular, metabolic and endocrine diseases in later life [8]. Cow energy status during gestation could also have an effect on the adaptive immune response of their progeny. ...
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This study aimed to evaluate the effects of undernutrition during the first third of gestation on cow-calf performance, immunological and physiological profiles during the next lactation in two cattle breeds. Fifty-three Parda de Montaña (PA) and 32 Pirenaica (PI) cows were inseminated, assigned to one of two diets (CONTROL or SUBNUT; 100% or 65% of their requirements) until day 82 of gestation, and fed 100% of the requirements during gestation and next lactation. Cow and calf performance were assessed during lactation. Colostrum and cow-calf plasma samples were analyzed to assess the passive transfer of immunoglobulins and to characterize energy metabolism. At calving, SUBNUT cows had a lower body condition score, which impaired most of the cow-calf parameters. All cows had considerable weight losses during lactation except for SUBNUT-PI cows. Colostrum immunoglobulin G (IgG) concentration was lower in SUBNUT-PI cows, and milk fat content was higher in SUBNUT cows. SUBNUT calves had lower values of body measurements at weaning, and calves born from SUBNUT-PI dams had lower milk intake and the lowest average daily gain (ADG), which was reflected in their lower plasma insulin-like growth factor-1 (IGF-1) concentration. In conclusion, undernutrition in early gestation in suckler cows had long-term effects on offspring postnatal growth, this physiological evidence being more severe in Pirenaica cow-calf pairs.
... However, these parameters can be permanently altered if some stimuli, such as poor nutrition, are present during fetal programming. During this critical and sensitive fetal stage, the structure, physiology, and metabolism of different organs and systems can be modified, leading to detrimental postnatal metabolic changes (Mossa, Walsh, Ireland, & Evans, 2015). Similarly, undernutrition during fetal life could cause permanent alterations in the endocrine function in the fetus to ensure fetus survival under adverse intrauterine conditions (Kiani et al., 2011;Rhind, 2004). ...
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This experiment evaluated the effects of subnutrition during early gestation on hematology in cows (Bos Taurus) and on hematological, metabolic, endocrine, and vitality parameters in their calves. Parda de Montaña and Pirenaica dams were inseminated and assigned to either a control (CONTROL, 100% requirements) or a nutrient‐restricted group (SUBNUT, 65%) during the first third of gestation. Dam blood samples were collected on days 20 and 253 of gestation, and calf samples were obtained during the first days of life. Pirenaica dams presented higher red series parameters than Parda de Montaña dams, both in the first and the last months of gestation. During early pregnancy, granulocyte numbers and mean corpuscular hemoglobin were lower in Pirenaica‐SUBNUT than in Pirenaica‐CONTROL cows. Calves from the SUBNUT cows did not show a physiological reduction in red series values in early life, suggesting later maturation of the hematopoietic system. Poor maternal nutrition affected calf endocrine parameters. Newborns from dystocic parturitions showed lower NEFA concentrations and weaker vitality responses. In conclusion, maternal nutrition had short‐term effects on cow hematology, Pirenaica cows showing a higher susceptibility to undernutrition; and a long‐term effect on their offspring endocrinology, SUBNUT newborns showing lower levels of IGF‐1 and higher levels of cortisol.
... With the exception of the results of Spratt and Leeson (1987), it could be hypothesized that the maternal effects of a reduction in the dietary CP level in the rearing phase only is not transferable to the progeny, but that the offspring performance can be influenced by applying the maternal dietary treatment during the laying phase. The latter seems also to be valid for research in rats, sheep, and cattle, in which even a distinction in effects on the next generation can be made based on the timing of the maternal treatment during the gestating and lactation periods (Zambrano et al., 2005;Mossa et al., 2015). Studies on the effects of the Dutch Hunger Winter also showed that maternal undernutrition during gestation had long-lasting effects in later life, but that these effects were dependent on the timing of the malnutrition during pregnancy (Roseboom et al., 2006). ...
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Several studies in mammals focused on the maternal programming of the metabolism by epigenetic mechanisms, while currently, the consequences of a maternal dietary treatment on the offspring performance of farm animals are of particular interest for commercial purpose. In the present study, we investigated if the zootechnical performance of the progeny was altered by a maternal dietary treatment, being a lower dietary crude protein (CP) of the grandparent and/or parent generation. The multigenerational effects of a reduced maternal CP content were investigated by reducing the dietary CP level by 25% in rearing and laying diets of pure line A breeders. The F0 generation breeders were fed either control (C) or reduced balanced protein (RP) diets. The F1 breeder generation was constructed by dividing the F0 female progeny again over a C or RP diet, resulting in 4 dietary treatments in the F1 generation: C/C, C/RP, RP/C, and RP/RP (letters indicating the diets in, respectively, F0 and F1 generations). The offspring performance was evaluated by a zootechnical and nitrogen retention trial on C and low-protein (LP) broiler diets. For the C broiler diet, the C/RP and RP/RP offspring were characterized by a higher BW from d 35 until d 42 compared to the C/C progeny, whereas the RP/C offspring had an intermediate BW that did not differ from the other groups. A tendency (P = 0.067) towards a better nitrogen retention was observed for the offspring of breeders that received the RP diets in F0 and/or F1 generation compared to the C/C progeny. For the LP broiler diet, the C/RP (P = 0.021) and RP/C (P = 0.001) offspring had a higher BW compared to the C/C progeny during the entire grow-out period. In addition, the C/RP offspring were characterized by a lower FCR from d 28 onwards (P = 0.021). In conclusion, dietary treatments imposed on mother hens can have direct effects on the next generation, as well as indirect effects on multiple generations.
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Methionine is an essential amino acid that contributes to protein formation, fetal development, and milk synthesis. Thus, we hypothesized that a supplementation with Optimethione® during the last third of gestation in female goats will increase the maternal body live weight, the milk yield and milk composition and the offspring weight and body mass index at birth and postnatal performance. We fed (n = 30) or not (n = 30) herbal methionine Optimethione® to pregnant mul-tiparous Alpine goats from gestational day 100 until delivery. We evaluated the productive var-iables from the dams and offspring. Maternal intake of herbal methionine Optimethione® dur-ing pregnancy did not increase the live weight or increase the milk yield and composition. However, the tested offspring variables were influenced by the maternal intake of herbal me-thionine Optimethione® during gestation by improving the birth weight, body mass index, and postnatal growth pattern. An increase in birth weight would be expected to increase neonatal survival up to weaning. Moreover, a relative fatness is required for reproductive success; thus, offspring that are born heavier and bigger can display a faster postnatal growth and accelerate the onset of puberty and increase reproductive success.
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The mammalian embryo is sensitive to and adapts to its metabolic environment. The mother's metabolic health and nutrient availability, for example, can modulate the oviductal fluid composition and thus embryo development. In this project, we induced energetic stress in bovine embryos during early culture to observe the epigenetic responses associated with metabolic stress, using a treatment paradigm known to decrease blastocyst rates. Embryos were generated using oocytes from slaughtered cows, and then exposed to an elevated glucose concentration (5 mM versus 0.2 mM in control conditions) for the first 3 days post-fertilization, followed by normal media until the blastocyst stage. The EmbryoGENE platform was then used to identify DNA methylation differences between the two treatments. Probes (450,000) were then analysed based on their genome location and methylation differences. Our results revealed that elevated glucose led to hypomethylation close to telomeric regions and methylation changes on genomic regions associated with energy metabolism. This article is protected by copyright. All rights reserved
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Maternal periconceptional undernutrition is associated with altered development and increased risks of adverse outcomes in the offspring. This circumstance is normal in flocks under extensive farming systems, which depend on natural forage resources. The aim of this study was to determine the effect of periconceptional undernutrition in sheep on behavioral and reproductive aspects of the offspring. Eighty ewes were synchronized in estrus and allocated to two groups (n=40) to be fed diets that provided 1.5 (C) or 0.5 (L) times the requirements for maintenance. Ewes were mated and 7 days later fed the control diet until lambing. One month after lambing, 32 lambs were exposed to tests to determine their cognitive and emotional responses. Six ewe lambs were euthanized and in vitro maturation and fertilization procedures were performed. L ewes presented a significant reduction in prolificacy and fecundity (P<0.05) in comparison with C ewes. Mean LW at lambing of L lambs was significantly higher than C lambs (C: 3.80±0.11; L: 4.24±0.15 kg, P<0.05). Lambs born from C ewes spent more time walking than L lambs (P<0.05) in the isolation test, revealing a decrease in the locomotor activity of lambs born from undernourished ewes around conception. Ewe lambs from the undernourished ewes presented a total population of oocytes 2.3 times higher than ovaries from control ewe lambs (60.0±7.8 v. 140.0±18.5 oocytes; P<0.05). In conclusion, periconceptional undernutrition is able to produce an increment in the body weight and the oocyte population, and an alteration of the locomotor activity of the offspring.
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Alterations to the metabolic environment in utero can impact subsequent female reproductive performance. Here, we used a model of rabbits receiving a high fat diet (H diet) (7.7% fat and 0.2% cholesterol) or a control diet (C diet) (1.8% fat, no cholesterol) from 10 weeks of age up to mating at 27 weeks and throughout gestation and lactation. At weaning at 5 weeks of age, F1 female offspring were placed on either C or H diet, resulting in a total of 4 groups C/C, C/H, H/C and H/H diet. Female offspring were mated between 18 and 22 weeks of age and euthanized at 28 days of gestation. A few days before mating and/or just before euthanasia, F1 females were fasted overnight, weighed and blood sampled for steroids and biochemistry. Organs were weighed at euthanasia and ovaries were collected. C/H and H/H F1 offspring had higher cholesterol and HDL plasma concentrations, together with a higher fat mass compared to C/C does, reflecting the effect of the postnatal diet, but no effect of the antenatal diet was observed on most parameters. The number of primordial, primary and secondary follicles were not different between groups but a significantly higher number of atretic follicles was observed in the C/H (P<0.001) and in the H/C (P<0.001) compared to control C/C ovaries, demonstrating both an effect of pre- and post-natal maternal nutrition. These data indicated that both maternal and post-natal high fat diet may induce follicular apoptosis but in this model the reproduction was not affected.
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Severe prenatal under nutrition is usually associated with low birth weights in offspring and disorders including hypertension, obesity and diabetes. Whether alterations in maternal nutrition insufficient to impair birth weight or prenatal growth impact the cardiovascular, stress or metabolic systems is unknown. In addition, little is known about the effects of maternal dietary restriction on development of the reproductive system in mammals. Here, we use the bovine model, which has a gestational length and birth rate similar to humans, to show that offspring from nutritionally restricted dams (during the first trimester) were born with identical birth weights and had similar post natal growth rates (to 95 weeks of age), puberty, glucose metabolism and responses to stress compared to offspring from control mothers. However, an increase in maternal testosterone concentrations was detected during dietary restriction and these dams had offspring with a diminished ovarian reserve (as assessed by a reduction in antral follicle count, reduced concentrations of anti-Müllerian hormone and increased follicle-stimulating hormone concentrations) enlarged aorta and increased arterial blood pressure compared with controls. Our study links transient maternal under nutrition and enhanced maternal androgen production with a diminished ovarian reserve and potential suboptimal fertility, enlarged aortic trunk size and enhanced blood pressure independent of alterations in birth weight, postnatal growth or stress response and glucose tolerance. The implications are that relatively mild transient reductions in maternal nutrition during the first trimester of pregnancy (even those that do not affect gross development) should be avoided to ensure healthy development of reproductive and cardiovascular systems in offspring.
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Maternal periconceptional undernutrition is associated with altered development and increased risks of adverse outcomes in the offspring. The aim of this work was to determine the effect of periconceptional undernutrition on behavioural and reproductive aspects of the offspring. Fifty ewes were synchronized in oestrus (day 0) and allocated to two groups (n = 25) to be fed diets that provided 1.5 (C) or 0.5 (L) times the requirements for maintenance until day 15. Ewes were mated and fed the control diet from day 16 until lambing. Two months after lambing, 26 lambs were exposed to tests to determine their cognitive/emotional responses. Six ewe lambs were euthanized and in vitro oocyte maturation and fertilization procedures performed. The experimental diets produced no changes of mean live weight (LW) of C ewes, L ewes presenting a reduction in their initial LW with significant differences at day 15, in comparison with C ewes (p < 0.05). L ewes experienced a significant reduction in their body condition (BC) in comparison with C ewes (p < 0.05). Fourteen days after the onset of the experimental diets, mean LW and BC of L ewes was significantly lower than those of C ewes (p < 0.05). Undernourished ewes presented a trend to a reduction of prolificacy and fecundity (p < 0.10) in comparison with C ewes. Emotional and cognitive test revealed a similar response between groups. Ewe lambs from the undernourished ewes presented a population of oocytes 1.7 times higher than ovaries from control ewe lambs (66.0 ± 0.73 vs. 113.7 ± 15.6 oocytes; p < 0.05) and had more oocytes in the 'good' (p < 0.05) and 'healthy' (p < 0.05) categories. In conclusion, a low plane of nutrition around conception significantly increases quantity and quality of the oocyte population of 60-day-old female descendants. Modifications of the cognitive and emotional responses of the progeny have not been evidenced.
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The concept of Developmental Origins of Health and Disease initially stemmed from the developmental programming of metabolic diseases. Reproductive functions and fertility in adulthood may also be programmed during foetal development. We studied the impact of dietary-induced maternal hyperlipidaemia and hypercholesterolaemia (HH), administered at 10 weeks of age and throughout the gestation and lactation, on male reproductive functions of rabbit offspring. Male rabbits born to HH dams and fed a control diet had significantly lighter testes and epididymes compared with rabbits born to control dams at adulthood. No significant changes in sperm concentration, sperm DNA integrity and sperm membrane composition were observed, but serum-free testosterone concentrations were decreased in HH males. This study confirms the importance of maternal metabolic status for the development of male reproductive organs.
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Maternal protein restriction during rat pregnancy and lactation is associated with alterations in reproductive function of female offspring including delayed onset of puberty, decreased fertility and premature reproductive aging. These alterations may be related to ovarian prepubertal development, distribution of follicle populations and their steroidogenic capacities. We undertook this study to evaluate the ovarian function of prepubertal female offspring exposed to maternal protein restriction during pregnancy and/or lactation. Adult female Wistar rats were fed a control (C-20% casein diet) or restricted isocaloric diet (R-10% casein) during pregnancy-first letter-and lactation-second letter, to form four groups, CC, RR, CR, RC. Ovaries were collected from 21-day-old female offspring. Preantral and antral follicles were quantified and mRNA expression of key genes involved in follicular development and steroidogenesis (gonadotropin receptors, StAR, P450scc and P450 aromatase) was evaluated. Serum gonadotropin levels were measured. Significantly decreased numbers of preantral and antral follicles were observed in CR and RC ovaries compared with CC. LH levels were lower and FSH higher in CR pups. mRNA expression of LH receptor (LH-R) was decreased in RR in comparison with the other groups. CR and RC expressed higher StAR, RC increased and RR decreased P450scc, whereas RR and CR decreased aromatase expression in comparison with CC. Maternal protein restriction influences prepubertal ovarian follicular number and steroidogenic function in the rat offspring, although RR and CR nutritional schemes have similar outcomes, the mechanisms affecting ovarian function are at different levels of the hypothalamic-pituitary-ovarian axis.
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