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ABSTRACT: When pregnant adolescent sheep are overnourished during pregnancy normal nutrient partitioning priorities to the gravid uterus are altered, leading to impaired placental development and fetal growth restriction. We hypothesized that decreasing dietary intake in overnourished dams during the final third of gestation may reverse this inappropriate nutrient partitioning in favor of the fetus. Adolescent ewes were offered control (C; n = 12) or high (H; n = 20) dietary intakes to induce normal vs. compromised placental development. Ten ewes receiving the H intake were switched to a low intake at d90 of gestation (HL). Between d90 to 130, HL dams lost weight and adiposity, and metabolic hormones and glucose at d130 were less than H and similar to C. In spite of these maternal changes, at d130 fetal bodyweight was equivalent in HL and H groups and ∼20% less than in C. A greater degree of brain sparing was evident in HL fetuses and glucose and insulin concentrations were more perturbed than in H fetuses. Relative to C, placentome weight was reduced by 46 and 32% in H and HL and the fetal:placentome weight ratio was H > HL > C. Placental vascular morphology was largely unaffected by maternal diet during late gestation but mRNA expression of five angiogenic genes was up-regulated in the fetal cotyledon of HL pregnancies, commensurate with blood vessel remodeling. Nevertheless, overfeeding to promote maternal anabolic growth during adolescent pregnancy impairs feto-placental development that cannot be rescued by reducing maternal intake during the final third of gestation.
Placenta 12/2011; 33(2):114-21. · 3.69 Impact Factor
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Ultrasound in Obstetrics and Gynecology 09/2011; 38(S1):23 - 23. · 3.01 Impact Factor
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ABSTRACT: Intra-uterine growth restriction (IUGR) predisposes obesity in adulthood. This may be due to altered fetal nutrition causing sustained changes within the developing hypothalamic energy balance regulatory system. Using our established ovine model of IUGR, 130-day singleton fetuses (term=147 days) were obtained from growing adolescent mothers on control dietary intake (C), high intake (H) or H with growth hormone administration during either early (H+early GH) or late gestation (H+late GH) (n=6/group). GH increased maternal glycemia for the duration of treatment. H and H+early GH fetuses showed IUGR compared with C fetuses; body weight was partially restored in H+late GH fetuses, with 40% increased adiposity. In the fetal hypothalamic arcuate nucleus (ARC), cocaine- and amphetamine-regulated transcript mRNA (anorexigenic) was decreased in H fetuses and correlated across all groups with total fetal liver glycogen. Neuropeptide Y, agouti-related peptide (orexigenic) and proopiomelanocortin (anorexigenic) mRNAs were not different between groups. Insulin receptor mRNA in the ARC was increased in H, H+early GH and H+late GH fetuses and correlated negatively with fetal plasma insulin. Leptin receptor mRNA in the ARC correlated positively with fetal plasma leptin concentration and fetal fat content. Therefore, in IUGR fetuses, a key anorexigenic neuropeptide is sensitive to altered glucose supply and the hypothalamic leptin-signaling pathway is altered prenatally by increased adiposity and leptinemia. These changes could impact on postnatal energy balance regulation.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 05/2011; 29(7):775-81. · 2.03 Impact Factor
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ABSTRACT: Peripubertal ewe lambs (44.3 +/- 1.1 kg of initial BW) were used in a 2 x 3 factorial design to test the effects of plane of nutrition (diet) and stage of gestation on maternal visceral tissue mass, intestinal cellularity, crypt cell proliferation, and jejunal mucosal vascularity. Singleton pregnancies to a single sire were established by embryo transfer, and thereafter ewes were offered a control (Control) or high (High) amount of a complete diet (2.84 Mcal/kg and 15.9% CP; DM basis) to promote slow or rapid maternal growth rates. After d 90 of gestation, feed intake of the Control group was adjusted weekly to maintain BCS and meet the increasing nutrient demands of the gravid uterus. Ewes were slaughtered at 50 d (n = 6 Control; n = 5 High), 90 d (n = 8 Control; n = 6 High), or 130 d (n = 8 Control; n = 6 High) of gestation. Ewes were eviscerated and masses of individual organs were recorded. The jejunum was sampled and processed for subsequent analyses. Final ewe BW for Control-fed ewes was similar at d 50 and 90 and increased (P = 0.10) from d 90 to 130 (46.0, 48.9, and 58.2 +/- 1.6 kg, respectively), whereas final BW increased (P <or= 0.01) throughout gestation in High-fed ewes (58.3, 68.8, and 81.1 +/- 1.6 kg, respectively). Relative jejunum mass (g/kg of maternal BW) was greater (P = 0.003) in Control-fed ewes compared with High-fed ewes and tended (P = 0.11) to decrease from d 50 to 130. There were diet x stage of gestation interactions (P <or= 0.08) for ileum and small intestinal total and relative weights. Ileum mass (g/kg of maternal BW) in Control-fed ewes was less (P = 0.07) compared with High-fed ewes at d 50, was equal (P = 0.19) to High-fed ewes at d 90, and was greater (P = 0.02) than High-fed ewes at d 130. Small intestine mass (g/kg of maternal BW) was similar between Control- and High-fed ewes at d 50 and 90, but Control-fed ewes had greater (P = 0.01) mass at d 130. Jejunal RNA and protein concentrations were less (P <or= 0.07) and DNA was unaffected (P = 0.43) in Control-fed compared with High-fed ewes. Stage of gestation did not affect jejunal RNA, DNA (mg/g), or protein concentrations. Jejunal cellular proliferation was not affected by diet or stage of gestation. In jejunal mucosal tissue, capillary number decreased, whereas capillary surface density and area per capillary increased (P = 0.01) with advancing pregnancy (d 50 vs. d 130), but were independent of diet. Data indicated that intestinal mass as a proportion of maternal BW declined in overnourished, gestating ewe lambs. This response was more pronounced during late gestation and is likely explained by the increasing maternal BW and adiposity rather than by the changing cellularity or cell proliferation.
Journal of Animal Science 10/2008; 87(1):222-35. · 2.10 Impact Factor
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ABSTRACT: Uterine blood flow (UtBF) is a major regulator of transplacental fetal nutrient supply. The aim was to serially measure uterine blood flow from mid to late pregnancy in a paradigm of relatively late onset placental and fetal growth restriction. Singleton bearing adolescent dams was fed high (H) or control (C) nutrient intakes to induce putatively compromised or normal pregnancies, respectively. A perivascular flow probe was attached to the uterine artery of the gravid horn on Day 83 of gestation and UtBF was then recorded continuously for 2h, three times weekly until approximately Day 135, when pregnancies were either terminated or ewes allowed to deliver at term (approximately Day 145). Pregnancy outcome was determined at term in contemporaneous ewes without UtBF assessment. Placental and fetal weights were lower (P<0.001) in H compared with C intake groups and were independent of flow probe surgery and monitoring. Uterine blood flow was lower in H compared with C groups at the first assessment (Day 88, P<0.001) and was positively correlated with adjusted fetal weight at term, irrespective of treatment group (P<0.01). UtBF increased throughout the second half of gestation in both groups. Linear regression analysis of UtBF against day of gestation revealed that the slope was equivalent (5.5 vs. 5.3ml/min per day) and the mean intercept lower (212 vs. 370ml/min, P<0.001) in H compared with C groups, respectively. This study demonstrates the feasibility of serially measuring UtBF within the same individual sheep for a protracted period during the second half of gestation. UtBF was already lower at mid gestation in putatively growth restricted compared with control pregnancies, ahead of any reduction in placental and fetal weight, but increased similarly during the second half of gestation in both groups. These data are commensurate with the reported decrease in placental angiogenic growth factor expression at mid gestation, and, indicate that attenuated UtBF is an early defect in this adolescent paradigm.
Placenta 06/2008; 29(8):718-24. · 3.69 Impact Factor
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ABSTRACT: The risks of miscarriage, prematurity and low birth weight are particularly acute in adolescent girls who are still growing at the time of conception. The role of maternal nutrition in mediating pregnancy outcome in this vulnerable group has been examined in sheep models. When singleton bearing adolescent dams are overnourished to promote rapid maternal growth throughout pregnancy, growth of both the placenta and fetus is impaired, and birth occurs prematurely relative to control adolescents of equivalent age. Studies at mid-gestation, prior to alterations in placental mass, suggest that reduced proliferation of the fetal trophectoderm, impaired angiogenesis, and attenuated uteroplacental blood flows are early defects in placental development. By late pregnancy, relative placental mass is reduced by 45% but uteroplacental metabolism and placental glucose transfer capacity remain normal when expressed on a placental weight specific basis. The asymmetrically growth-restricted fetuses are hypoxic, hypoglycemic and have reduced insulin and IGF-1 concentrations. Absolute umbilical nutrient uptakes are attenuated but fetal utilisation of glucose, oxygen and amino acids remains normal on a fetal weight basis. This suggests altered sensitivities to metabolic signals and may have implications for subsequent metabolic health. At the other end of the nutritional spectrum, many girls who become pregnant have inadequate or marginal nutritional status during pregnancy. This situation is replicated in a second model whereby dams are prevented from growing during pregnancy by relatively underfeeding. Limiting maternal intake in this way gradually depletes maternal body reserves leading to a lower transplacental glucose gradient and a modest slowing of fetal growth in late pregnancy. These changes appear to be independent of alterations in placental growth per se. Thus, while the underlying mechanisms differ, maternal intake at both ends of the nutritional spectrum is a powerful determinant of fetal growth in pregnant adolescents.
Placenta 05/2006; 27 Suppl A:S61-8. · 3.69 Impact Factor
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ABSTRACT: Overnourishing adolescent ewes throughout pregnancy promotes maternal tissue synthesis at the expense of placental growth, which in turn leads to a major decrease in lamb birth weight. As maternal dietary intakes are inversely related to peripheral progesterone concentrations in these adolescent dams, it was hypothesized that sup-optimal progesterone concentrations in overnourished dams may compromise the growth of the differentiating conceptus resulting in fewer uterine caruncles being occupied and, hence, fewer placentomes formed. This hypothesis was tested by supplementing overnourished adolescent dams with exogenous progesterone during early pregnancy and determining the impact on pregnancy outcome at term. Embryos recovered from superovulated adult ewes inseminated by a single sire were transferred in singleton to the uterus of peripubertal adolescent recipients. After transfer of embryos, ewes were offered a moderate or high amount of a complete diet (n=11 per group). A further high intake group received a progesterone supplement each day from day 5 to day 55 of gestation (term=145 days) to restore circulating progesterone concentrations to moderate values throughout the first third of pregnancy (n=11). For ewes establishing pregnancies (n=7 per group), live weight gain during the first 100 days of gestation was 66+/-4, 323+/-17 and 300+/-7 g per day, body condition score at term was 2.1+/-0.05, 3.0+/-0.08 and 3.1+/-0.07 units and the duration of gestation after spontaneous delivery was 148+/-1.7, 144+/-0.8 and 143+/-0.8 days for the moderate intake, high intake and high intake plus progesterone groups, respectively. At delivery, fetal cotyledon mass (136+/-12.1 versus 57+/-8.2g, P<0.001) and lamb birth weight (5164+/-151 versus 2893+/-381 g, P<0.001) were higher in moderate intake than in high intake dams. Progesterone supplementation restored circulating concentrations to moderate values during the first third of gestation. Lamb birth weight in the high intake plus progesterone group (4150+/-389 g) was intermediate between the high intake (P<0.02) and moderate intake (P<0.05) groups, but this change in birth weight was not associated with corresponding changes in fetal cotyledon mass (76+/-10.3 g). Moreover, the number of fetal cotyledons was similar in all three groups. Thus, progesterone did not directly affect the growth of the fetal cotyledon but may have influenced placental vascularity, blood flow or nutrient transfer capacity or alternatively the development of the embryonic inner cell mass.
Reproduction (Cambridge, England) 10/2003; 126(4):481-7. · 3.09 Impact Factor
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ABSTRACT: The influence of maternal nutrition during pregnancy on anterior pituitary gonadotrophin gene expression and ovarian development in sheep fetuses during late gestation was investigated. Embryos recovered from superovulated adult ewes that had been inseminated by a single sire were transferred, singly, into the uteri of adolescent recipients. After embryo transfer, adolescent ewes were offered a high or moderate amount of a complete diet. Pregnancies were terminated at day 131 +/- 0.6 of gestation and the fetal brain, anterior pituitary gland and gonads were collected. Gonadotrophin gene expression (LHbeta and FSHbeta subunits) in the fetal pituitary gland was examined using in situ hybridization. Ovarian follicular development was quantified in haematoxylin- and eosin-stained ovarian sections embedded in paraffin wax. Six dams that were offered a high nutrient intake carried normal-sized fetuses (weight within +/- 2 SD of mean weight for control fetuses from dams fed a moderate level of complete diet) and 13 dams carried growth-restricted fetuses (weight <or= +/- 2 SD of mean weight for control fetuses from dams fed a moderate level of complete diet). Mean placental masses in these groups were 354 +/- 24.5 and 230 +/- 21.1 g, respectively, compared with 442 +/- 54.3 g in the dams that were offered a moderate nutrient intake (n = 6). Growth-restricted fetuses from dams offered a high nutrient intake showed higher pituitary LHbeta mRNA expression (P < 0.05) than normal-sized fetuses from dams offered a moderate nutrient intake (252 +/- 21.6 and 172 +/- 23.6 nCi g(-1), respectively). FSHbeta mRNA expression was not influenced by growth status. Fewer follicles (primarily in the resting pool) were observed in the ovaries of both growth-restricted (P < 0.002) and normal-sized fetuses from dams offered a high nutrient intake (P < 0.01) compared with normal-sized fetuses from dams offered a moderate nutrient intake. Irrespective of nutritional treatment, the total number of follicles was positively associated with placental mass (P < 0.01). Thus, a high maternal nutrient intake during adolescent pregnancy had a negative influence on ovarian follicular development in fetuses as determined during late gestation.
Reproduction (Cambridge, England) 07/2002; 123(6):769-77. · 3.09 Impact Factor
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ABSTRACT: The onset of puberty in prenatally growth-restricted versus normally grown lambs of both sexes, born in April and housed under natural photoperiod, was examined. Singleton pregnancies were established and adolescent ewes were offered a high or moderate nutrient intake throughout gestation. Placental mass was reduced (P < 0.001) in high compared with moderate intake dams and resulted in the birth of growth-restricted and normal birth weight offspring, respectively. At birth, female lambs weighed 3.43 kg versus 5.03 kg (P < 0.001; n = 14 per group) and male lambs weighed 2.75 kg versus 5.18 kg (P < 0.001; n = 7 per group) in growth-restricted and normal birth weight groups, respectively. Lambs suckled for 12 weeks and thereafter were fed ad libitum until week 43 of age. Growth-restricted lambs had lower preweaning live weight gains and this difference was more pronounced in male (P < 0.05) than in female lambs (P = 0.07). Thereafter, live weight remained lower (P < 0.05) in growth-restricted than in normally grown lambs of both sexes until week 25 of age. In females, the time of onset of puberty was similar in the two groups. All females ovulated and there were no differences in the number of ovarian cycles recorded or in the incidence of aberrant ovarian function. In males, testosterone concentrations and testicular volume were lower in growth-restricted compared with normally developed lambs from birth until weeks 28 and 35 of age, respectively (P < 0.05). The seasonal increase in plasma testosterone concentrations occurred later in growth-restricted than in normally developed lambs (P < 0.01) but the timing of maximum peak concentrations was similar. Peak testosterone concentrations were lower (P < 0.05) in growth-restricted than in normal male lambs.
Reproduction (Cambridge, England) 09/2001; 122(3):375-83. · 3.09 Impact Factor
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ABSTRACT: This study examined the pattern of circulating leptin in age-matched sheep during adolescent pregnancy, and its relationship with maternal dietary intake, body composition and tissue expression of the leptin gene. Overfeeding the adolescent pregnant ewe results in rapid maternal growth at the expense of the placenta, leading to growth restriction in the fetus, compared with normal fed controls. Our results demonstrate that, in the adolescent ewe, overfeeding throughout pregnancy was associated with higher maternal leptin concentrations, when compared with moderately fed controls (P<0.05), with no peak in circulating leptin towards the end of pregnancy. There was a close correlation between indices of body composition and circulating leptin levels at day 104 of gestation and at term (P<0.03). Further, when the dietary intake was switched from moderate to high, or high to moderate, at day 50 of gestation, circulating leptin levels changed rapidly, in parallel with the changes in dietary intake. Leptin mRNA levels and leptin protein in perirenal adipose tissue samples, taken at day 128 of gestation, were higher in overfed dams (P<0.04), suggesting that adipose tissue was the source of the increase in circulating leptin in the overnourished ewes. Leptin protein was also detected in placenta but leptin gene expression was negligible. However, leptin receptor gene expression was detected in the ovine placenta, suggesting that the placenta is a target organ for leptin. A negative association existed between maternal circulating leptin and fetal birth weight, placental/cotyledon weight and cotyledon number. In conclusion, in this particular ovine model, hyperleptinaemia was not observed during late pregnancy. Instead, circulating leptin concentrations reflected increased levels of leptin secretion by adipose tissue primarily as a result of the increase in body fat deposition, due to overfeeding. However, there appears to be a direct effect of overfeeding, particularly in the short term. In the nutritional switch-over study, circulating leptin concentrations changed within 48 h of the change in dietary intake. The presence of leptin protein and leptin receptor gene expression in the placenta suggests that leptin could be involved in nutrient partitioning during placental and/or fetal development.
Journal of Endocrinology 06/2001; 169(3):465-76. · 3.55 Impact Factor
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ABSTRACT: The aim of the present study was to investigate the effects of administering a high plane diet during early to mid-gestation on the uterine and placental insulin-like growth factor (IGF) system and on systemic IGF-I concentrations in pregnant adolescent ewes with restricted placental growth. Embryos recovered from superovulated ewes inseminated by a single sire were transferred in singleton to the uterus of adolescent recipients. After transfer ewes were offered a high (H) or moderate (M) amount of a complete diet calculated to promote rapid or normal maternal growth rates, respectively. Five ewes from each group were switched from either M to H or H to M diets at day 52 of gestation. Maternal and fetal blood samples and placental tissues were collected from all animals at day 104. Ewes on the high plane diet from mid-gestation (HH, MH groups) had restricted placental mass (P < 0.01) and tended to have smaller fetuses. This was associated with increased maternal plasma IGF-I concentrations (P < 0.001). The pattern of expression of components of the IGF system in the uterus and placenta was studied by in situ hybridization. IGF-I mRNA concentrations were below the limit of detection. IGF-II mRNA expression was high in the fetal mesoderm and present in maternal stroma, but was not influenced by nutritional treatment. In contrast, IGF binding protein 1 (IGFBP-1) mRNA expression was higher (P < 0.05) and IGFBP-3 mRNA expression was lower (P < 0.05) in the endometrial glands of ewes in HH and MH groups. In the fetal trophoblast, IGFBP-3 mRNA expression was higher in the MH group. Type 1 IGF receptor expression was increased (P < 0. 01) in the luminal epithelium of the HM group and IGFBP-2 mRNA expression was highest in the placentome capsule of ewes in the HH group. Together, these results indicate that reprogramming of the uterine and placental IGF axis by maternal nutrition could contribute to placental growth retardation in growing adolescent sheep.
J Reprod Fertil 03/2000; 118(2):407-16.
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ABSTRACT: The aim was to investigate the consequences of nutritionally-mediated placental growth restriction on fetal organ growth, conformation, body composition and endocrine status during late gestation. Embryos recovered from superovulated adult ewes inseminated by a single sire were transferred in singleton to the uterus of peripubertal adolescent recipients. Post-transfer, adolescent dams were offered a high (H) or moderate (M) level of a complete diet to promote rapid or moderate maternal growth rates, respectively (n=7 per group). After day 100 of gestation the feed intake of the M dams was adjusted weekly to maintain body condition score. Liveweight gain during the first 100 days of gestation was 301+/-24 and 90+/-4.6 g/day for the H and M groups, respectively. Maternal plasma concentrations of insulin, IGF-I and urea were significantly higher and non-esterified fatty acid concentrations significantly lower in H compared with M dams prior to slaughter on day 128 of gestation. At this stage of gestation, total placentome weight was 50 per cent lower in H compared with M groups (P< 0.001) and was associated with a 37 per cent reduction in fetal weight (P< 0.01). All variables of fetal conformation and absolute fetal organ weights, with the exception of the adrenal glands, were lower (P< 0. 05) in the fetuses from H intake dams. However, relative fetal organ weights expressed as g/kg fetal body weight, with the exception of the gut, were not influenced by maternal dietary intake. Furthermore, fetal weight but not maternal nutritional group were predictive of individual organ weight for all organs dissected. Together these results imply that growth restriction in the fetuses derived from H intake dams was largely symmetrical. Fetal plasma concentrations of insulin, IGF-I and glucose were attenuated (P< 0.05) in fetuses from H compared with M groups. The lower fetal body weight in the former group was associated with a reduction in absolute but not relative crude protein (P< 0.01) and fat content (P< 0.05). Total fetal liver glycogen content but not concentration was (P< 0.05) reduced in H versus M groups. The lower mass of both the placenta and fetal liver was due to a reduction in cell number rather than an alteration in cell size. Thus, over-nourishing adolescent sheep is associated with a major restriction in placental growth which mediates a gradual slowing of fetal growth during the final third of pregnancy.
Placenta 02/2000; 21(1):100-8. · 3.69 Impact Factor
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ABSTRACT: The aim was to investigate whether placental growth and hence pregnancy outcome could be altered by switching adolescent dams from a high to a moderate nutrient intake, and vice-versa, at the end of the first trimester. Embryos recovered from adult ewes inseminated by a single sire were transferred in singleton to peripubertal adolescents. After transfer, adolescent ewes were offered a high (H, n = 33) or moderate (M, n = 32) level of a diet calculated to promote rapid or moderate maternal growth rates, respectively. At Day 50 of gestation, half the ewes had their dietary intakes switched, yielding 4 treatment groups: HH, MM, HM, and MH. A subset of ewes were killed at Day 104 of gestation to determine maternal body composition in relation to growth of the products of conception. Maternal body composition measurements revealed that the higher live weight in the high-intake dams was predominantly due to an increase in body fat deposition, with a less pronounced increase in body protein. At Day 104, HH and MH groups (high intake during second trimester) compared with MM and HM groups (moderate intake during second trimester) had a lower (p < 0.002) total fetal cotyledon weight; but fetal weight, conformation, and individual organ weights were not significantly influenced by maternal dietary intake. In ewes delivering live young at term, a high plane of nutrition from the end of the first trimester (HH and MH groups) compared with moderate levels (MM and HM groups) was associated with a reduction in gestation length (p < 0.009), total placental weight (p < 0.002), total fetal cotyledon weight (p < 0.001), and mean fetal cotyledon weight per placenta (p < 0.001). Fetal cotyledon number was dependent on maternal dietary intake during the first trimester only and was lower (p < 0.007) in HH and HM ewes compared to MM and MH ewes. The inhibition of fetal cotyledon growth in HH and MH groups was associated with a major decrease (p < 0.001) in lamb birth weight at term relative to the MM and HM groups. Thus, reducing maternal dietary intake from a high to a moderate level at the end of the first trimester stimulates placental growth and enhances pregnancy outcome, and increasing maternal dietary intake at this time point has a deleterious effect on placental development and fetal growth.
Biology of Reproduction 08/1999; 61(1):101-10. · 4.01 Impact Factor
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ABSTRACT: Inappropriate maternal nutrient intake at key developmental timepoints during ovine pregnancy has a profound influence on the outcome of pregnancy and aspects of postnatal productivity. However, the responses to alterations in maternal nutrition in adult sheep are often highly variable and inconsistent between studies. The growing adolescent sheep provides a new, robust and nutritionally sensitive paradigm with which to study the causes, consequences and reversibility of prenatal growth restriction. Overnourishing the adolescent dam to promote rapid maternal growth throughout pregnancy results in a major restriction in placental mass, and leads to a significant decrease in birthweight relative to moderately fed, normally growing adolescents of equivalent gynaecological age. Maternal insulin and IGF-I concentrations are increased from an early stage of gestation in overnourished adolescent dams and these hormones ensure that the anabolic drive required to promote maternal tissue synthesis is initiated at a time when the nutrient requirements of the gravid uterus are low. The major restriction in fetal growth in rapidly growing dams occurs irrespective of high concentrations of essential nutrients in the maternal circulation and suggests that the small size or altered metabolic and transport capacity of the placenta is the primary constraint to fetal growth. The decrease in placental weight in the overnourished animals reflects a significant reduction in both fetal cotyledon number and mean cotyledon weight. The role of nutritionally mediated alterations in progesterone and the components of the IGF system in this early pregnancy placental phenomenon are being investigated. Nutritional switch-over studies have demonstrated that reducing maternal nutrient intake at the end of the first third of pregnancy can stimulate placental growth and enhance pregnancy outcome, but increasing nutrient intake at this time has a deleterious effect on placental development and fetal growth.
Journal of reproduction and fertility. Supplement 02/1999; 54:385-99.
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ABSTRACT: The objective of this study was to determine the relative importance of seasonal changes in ovulation rate, fertilization rate and embryo survival as the cause of reduced lambing rates in ewes mated in February compared with those mated in November. The study was conducted at 57 degrees N using mature Mule ewes and Suffolk rams. Sixty ewes were allocated equally to five groups: unbred (UB) or mated at a natural oestrus during November (N) or February (F) by natural (N) or cervical artificial (A) insemination. Groups were maintained separately at pasture supplemented with hay. A raddled vasectomized or non-vasectomized ram was present with UB, NN and NA groups from 26 October 1995 to 1 January 1996 and with UB, FN and FA groups from 25 January 1996 to 31 March 1996. Ewes marked by the ram were recorded twice a day, and those in groups NN, NA, FN and FA were inseminated at their second behavioural oestrus. For all ewes, blood samples were obtained once a day from introduction of the vasectomized rams until 30 days after mating (groups NN, NA, FN and FA) or 20 days after the first oestrus (group UB), and ovulation rate was measured by laparoscopy 7 days after the first oestrus. For ewes in groups NN, NA, FN and FA, ovulation rate was measured again after the second oestrus and ova were recovered from six ewes per group for assessment of fertilization before autotransfer. Pregnancy and lambing rates were recorded at term. Mean (+/- SE) dates of the first recorded oestrus for ewes in groups NN, NA and UB, and FN, FA and UB were 4 +/- 1.1 November and 4 +/- 0.9 February, respectively, and intervals between the first and second oestrus were 16 +/- 0.2 and 17 +/- 0.3 days (P < 0.01), respectively. Ovulation rates were 2.6 +/- 0.08 and 2.0 +/- 0.05 (P < 0.001), and peripheral progesterone concentrations during the luteal phase were 8.5 +/- 0.25 and 7.6 +/- 0.31 ng ml-1 (P < 0.05), for November and February, respectively. The difference in peripheral progesterone concentration was not solely attributable to the difference in ovulation rate. There was no significant effect of month or method of insemination, or of embryo recovery and autotransfer procedures on pregnancy rates and the proportion of ewes that became pregnant were NN 0.92, NA 0.83, FN 0.67 and FA 0.75. For ewes undergoing embryo recovery and autotransfer, ova recovered per corpus luteum were 1.00, 0.93, 1.00 and 0.92, fertilized ova per ovum recovered were 0.69, 0.92, 1.00 and 0.83, and lambs born per corpus luteum were 0.62, 0.79, 0.78 and 0.58 for NN, NA, FN and FA groups, respectively. There were no significant seasonal effects on fertilization rate or embryo survival. It is concluded that a seasonal decline in ovulation rate is the primary cause of reduced lambing rates in ewes mated in February compared with those mated in November. Pregnancy rates were high after mating in both periods and were not enhanced by the use of cervical insemination.
J Reprod Fertil 01/1999; 115(1):133-40.
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ABSTRACT: From days 4-104 of pregnancy, adolescent sheep, weighing 43.7 (SE 0.87) kg were offered a complete diet at two different intakes (approximately 5 or 15 kg/week) designed to meet slightly, or well above, maternal maintenance requirements. The fetal and maternal muscles were taken on day 104 of pregnancy and analysed for total DNA, RNA and protein. Ewes offered a high intake to promote rapid maternal weight gain, weighed more (76.5 (SE 4.5) v 50.0 (SE 1.7) kg) and had muscles with a greater fresh weight, whilst their fetuses had smaller muscles, than those fed at a lower intake. Plantaris muscle of the ewes fed at the high intake contained more RNA and protein; again the opposite situation was found in the fetal muscle. On the higher maternal intakes, the DNA, RNA and protein contents of the fetal plantaris muscle were less than in fetuses of ewes fed at the lower intake. To investigate the possible mechanisms involved in this decrease in fetal muscle mass, cytosolic and membrane-associated muscle proteins were subjected to Western immunoblotting with antibodies to nine isoforms of protein kinase C (PKC), a family of enzymes known to play an important role in cell growth. Five PKC isoforms (alpha, epsilon, theta, mu, zeta) were identified in fetal muscle. One of these, PKC-alpha was located predominantly in the cytosolic compartment in the smaller fetuses of the ewes fed at a high plane of nutrition, but was present to a greater extent in the membranes of the more rapidly growing fetuses of the ewes fed at the lower intake. This was the only isoform to demonstrate nutritionally related changes in it subcellular compartmentation suggesting that it may mediate some aspects of the change in fetal growth rate.
British Journal Of Nutrition 05/1998; 79(4):351-7. · 3.01 Impact Factor
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ABSTRACT: Thirty-two Border Leicester x Scottish Blackface ewes that lambed in March were individually penned with their lambs from April 16th and given daily an oral dose of 3 mg melatonin at 1500 h (Group M). A further 32 acted as controls (Group C). Within each group half were used as embryo donors (Group D) following superovulation and half received embryos (Group R) following an induced estrus. Prior to weaning on 21 May ewes received ad libitum a complete diet providing 9 megajoules (MJ) of metabolizable energy and 125 g/kg crude protein. Thereafter each received 1.6 kg of the diet daily. In early June each ewe received an intravaginal device (300 mg progesterone) inserted for 12 d. Donors were superovulated with 4 i.m. injections of porcine FSH 12 h apart, commencing 24 h before progesterone withdrawal. Ovulation in recipients was induced with 800 IU PMSG injected i.m. at progesterone removal. Donor ewes were inseminated 52 h after progesterone withdrawal. Embryos were collected 4 d later and transferred to recipients. Melatonin suppressed plasma prolactin (P < 0.001) and advanced estrus (P < 0.05) and timing of the LH peak (P < 0.05). These events also occurred earlier in donors than in recipients (P < 0.01). Mean (+/- SEM) ovulation rates for melatonin-treated and control donors were 5.5 +/- 0.71 and 4.7 +/- 0.66, respectively (NS). Corresponding recipient values were 3.3 +/- 0.40 and 3.4 +/- 0.39 (NS). Mean (+/- SEM) embryo yields were 2.9 +/- 0.64 and 2.6 +/- 0.73 for melatonin-treated (n = 15) and control (n = 16) donors, respectively, and for the 12 ewes per treatment that supplied embryos, corresponding numbers classified as viable were 2.7 +/- 0.47 and 2.3 +/- 0.61 (NS). Following transfer, 57% of embryos developed to lambs when both donor and recipient received melatonin, 86% when only the donor received melatonin, 91% when only the recipient received melatonin, and 67% when neither received melatonin (NS). Thus, embryo survival following transfer was not improved by treating recipients with melatonin. Gestation length and lamb birthweights were unaffected by melatonin. Unlike nonpregnant control ewes, melatonin-treated recipients that failed to remain pregnant sustained estrous cyclicity following embryo transfer.
Theriogenology 04/1998; 49(5):943-55. · 1.96 Impact Factor
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ABSTRACT: It has previously been reported that high nutrient intakes which promote rapid maternal growth throughout pregnancy are associated with poor pregnancy outcome when compared with normally growing adolescent animals. The present study examined the maternal plasma concentrations of a number of putative endocrine regulators of nutrient partitioning between the maternal and fetal compartments in relation to placental and fetal growth in this novel experimental paradigm. Embryos were recovered on day 4 after oestrus from superovulated adult ewes that had been inseminated using semen from a single sire and synchronously transferred, in singleton, to the uterus of peripubertal adolescent recipients (n = 38), which had been induced to ovulate at 32 weeks of age (live weight 47.4 +/- 0.4 kg). Post-transfer, the adolescent recipients were offered a high (n = 21) or moderate (n = 17) level of a complete diet calculated to achieve rapid (RMG) or normal (NMG) maternal growth rates. After day 100 of gestation, the feed intake of the NMG group was adjusted weekly to meet the increasing nutrient demands of the gravid uterus. Pregnancy rate following embryo transfer was higher (P < 0.05) in the RMG (90%) than in the NMG (59%) group. For ewes delivering live young at term, liveweight gain during the first 100 days of gestation was 294 +/- 12.9 and 84 +/- 4.7 g/day for the RMG (n = 16) and NMG (n = 10) groups respectively, and body condition score immediately prior to parturition was higher in RMG than in NMG ewes (2.9 +/- 0.04 vs 1.9 +/- 0.15 score units respectively, P < 0.001). For the RMG and NMG groups respectively, mean placental weight was 327 +/- 18.1 and 485 +/- 16.6 g with lamb birth weights of 3.49 +/- 0.13 and 4.82 +/- 0.21 kg (P < 0.001). The reduction in placental mass in the RMG group reflected a decrease in the number (P < 0.001) and size (P < 0.01) of the fetal cotyledons. The duration of gestation was shorter (P < 0.001) and colostrum yield at parturition lower (P < 0.001) in the RMG group. Maternal insulin concentrations, determined three times weekly, were higher (P < 0.001) throughout gestation in the RMG group and irrespective of treatment group were negatively correlated (P < 0.01) with placental weight and lamb birth weight. High glucose levels throughout gestation and a decreased response to an exogenous insulin challenge on day 95 of gestation implied a degree of insulin resistance in the RMG group but, in spite of these high maternal glucose concentrations, the reduced size of the placenta probably constrained fetal growth. Maternal IGF-I levels determined weekly, were elevated (P < 0.001) during the second and third trimester in RMG versus NMG groups and a sustained elevation in maternal tri-iodothyronine and thyroxine concentrations was evident in the RMG group from mid-gestation. In contrast, GH pulse frequency and mean GH concentrations, determined on day 68 and 122 of gestation, were lower (P < 0.05) in the RMG group, and irrespective of treatment group, were correlated negatively with feed intake and positively with placental weight and colostrum yield at parturition. Progesterone concentrations were lower in the RMG group during the second and third trimesters (P < 0.001) and, irrespective of treatment group, were positively associated (P < 0.001) with placental weight, gestation length and colostrum yield. These results suggest that in pregnant adolescent sheep on high dietary intakes, elevated insulin and IGF-I levels ensure that the anabolic drive to maternal tissue synthesis is established during early gestation at the expense of placental growth. The consequent restriction in placental transport capacity is the primary limitation to fetal growth and reduced GH and placental progesterone secretion may impair colostrum production.
Journal of Endocrinology 11/1997; 155(2):359-68. · 3.55 Impact Factor
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ABSTRACT: Postnatal photoperiodic experience plays a pivotal role in determining the timing of ovarian activity in female lambs. This study examines whether a photoperiodic history gained while in utero is able to influence this timing. Pregnant Soay ewes were maintained in either long days (n = 7, 18 h light: 6 h dark; group PLD) or short days (n = 12, 6 h light: 18 h dark; group PSD) from 25 days of gestation. At birth, female lambs (n = 8 per group) were transferred to long days for 10 weeks, and then placed under short days until the end of the experiment at 38 weeks of age. Blood samples were collected from lambs on the day of birth and three times weekly for the duration of the study and the resulting plasma assayed for progesterone and prolactin. Although both gestational photoperiods produced, at best, abbreviated periods of ovarian activity, lambs born to ewes which experienced long days during gestation (group PLD) exhibited elevated plasma progesterone concentrations significantly earlier (P < 0.05) than lambs born to ewes exposed to short days during gestation (group PSD) (mean +/- SEM, 193 +/- 17 versus 244 +/- 14 days for PLD and PSD groups, respectively. Plasma prolactin concentrations in newborn lambs born between late December and early April were not affected by the ambient photoperiod, but reflected the artificial daylength experienced by their mothers during gestation. Lambs born to ewes maintained under long days during gestation (group PLD) had significantly higher prolactin concentrations on the day of birth than lambs born to ewes maintained under short days during gestation (group PSD) (45 +/- 5.4 ng/ml versus 7 +/- 3.7 ng/ml respectively, P < 0.001). The mean birth weight, rate of live weight gain and live body weight of lambs at the end of the experiment did not vary significantly between treatment groups. These results suggest that the ovine foetus is sensitive to photoperiodic information prior to birth, and develops a photoperiodic history which, under the present experimental conditions, modulates the subsequent endocrine status of the neonatal lamb.
Animal Reproduction Science 07/1997; 47(4):303-14. · 1.75 Impact Factor
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ABSTRACT: In the first of two experiments investigating the effect of dietary urea on the survival and metabolism of ovine embryos, 30 Border Leicester x Scottish Blackface ewes received a maintenance diet (milled hay, molasses, minerals, vitamins) with no urea (control, C; n = 10) or with added urea at 15 g (low urea, LU; n = 10) or 30 g (high urea, HU; n = 10) kg-1 feed for a 12 week period. The degraded nitrogen (N) status relative to estimated rumen microbial N requirements was -2, +9 and +20 g per day, respectively. One week after allocation to diets, progesterone priming (12 days) commenced. Ewes received 800 IU of equine chorionic gonadotrophin at progesterone withdrawal, were inseminated 52 h later (Day 0) and embryos were collected from five ewes per group at Day 4 and from five ewes at Day 11. If available, one embryo was returned to each ewe; the rest were cultured in vitro. There was no effect of treatment on progesterone, luteinizing hormone (LH), or time of oestrus onset C, LU and HU plasma urea (P < 0.001) and ammonia levels (C vs. HU, P < 0.01; LU vs. HU, P < 0.05) differed. Day 4 HU embryos were retarded relative to C and LU embryos. After 3 days of culture, 70%, 66% and 0% of C, LU and HU embryos, respectively, were viable. Mid-term pregnancy rates following transfer were 63%, 43% and 33%. Only one HU lamb (male) was born following embryo transfer, its birthweight (10.1 kg) exceeded that of its C (n = 3; 7.0, 7.0, 7.5 kg) and LU (n = 2; 7.3, 8.2 kg) counterparts (P < 0.025). In the second experiment, C2 (2.5 g urea kg-1; n = 5) and HU2 (30 g kg-1; n = 7) diets which provided similar intakes of degraded N relative to microbial requirements as those for C and HU ewes in Experiment 1 were fed to Border Leicester x Scottish Blackface ewes superovulated with 16 mg of porcine follicle-stimulating hormone. Urea and ammonia levels in utero-oviductal samples were elevated in HU2 ewes (P < 0.05). At collection (Day 3), HU2 embryos used more glucose (P < 0.01) and, following culture, some exhibited up to a 2.8-fold increase in metabolism. In conclusion, excess rumen degradable N in ewe diets elevates urea and ammonia in plasma and in utero, with an associated increase in embryo mortality. Nevertheless, metabolism appears to be up-regulated in some embryos and, among those that survive, fetal growth appears to be enhanced.
Animal Reproduction Science 05/1997; 47(1-2):71-90. · 1.75 Impact Factor
