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.

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.