Modifications in maternal nutrition during pregnancy can significantly disrupt fetal growth and subsequent post-natal health and survival. This study investigated the effects of undernutrition on fetal growth and the potential mechanisms involved. Tissue from pregnant ewes (n=27) was investigated on days 45, 90 and 135 of gestation (term=150 days). The thoracic girth (P<0·05) was greater in fetuses from nutrient restricted ewes on day 45 and there was also a trend towards an increased gut weight (P<0·08). By day 90, the fetal brain and thymus weight were lighter in underfed than in well-fed animals whilst the weight of the fetal ovaries was heavier (P<0·05). On day 135 the fetal heart, pancreas, thymus, gut and kidney weights were lighter in undernourished ewes (P<0·05). When expressed as a percentage of fetal body weight, significance was retained in the heart, pancreas and thymus (P<0·05). Bone growth was also affected. At day 90 the fetal femur and metatarsal were longer in underfed mothers (P<0·05). In contrast, the fetal humerus and scapula were shorter in underfed than in well-fed animals on day 135 (P<0·05) when the weight of the semitendinosus muscle (P<0·05) was also reduced. The fall in fetal glucose (P<0·1), insulin (P<0·01) and IGF-I (P<0·01) levels in underfed ewes on day 135 may have compromised fetal growth. Fetal plasma IGF binding protein-2 also increased between days 90 and 135 in underfed ewes (P<0·03), whilst levels were unaltered in well-fed animals. Although maternal and fetal plasma IGF-I levels increased with gestation (P<0·01) and the placentome morphology altered in all ewes (P<0·05), the fall in placental mass (P<0·05), amniotic and allantoic glucose concentrations (P<0·05) and maternal plasma glucose and insulin levels (P<0·05) in underfed ewes in late gestation may have compromised fetal substrate delivery. These perturbations in fetal development may have significant implications on adult health and carcass conformation, raising important health and economic issues in medical and agricultural sectors.

The placenta is a highly efficient multifunctional organ, mediating the exchange of nutrients, gases and waste products between the dam and fetus. This study investigated the effects of chronic maternal undernutrition (70% of estimated requirement) on the placental growth trajectory in the ewe on days 45, 90 and 135 of gestation. The insulin-like growth factor (IGF) system was investigated using in situ hybridisation analysis to determine if nutritionally mediated alterations in placental growth were regulated through modifications in placental IGF expression. Placental weight increased between days 45 and 90 (P,0·01), accompanied by a reduction in maternal placentome IGF binding protein (IGFBP)-3, -5 and -6 expression (P,0·05), although IGF-II mRNA levels in maternal villi remained unchanged. Placentome number was unaffected by diet or gestational age. Placental weight remained constant between days 90 and 135 in ewes on 100% maintenance rations but decreased over this period (P,0·05) in ewes on the 70% rations. Gross morphology also altered, so the underfed ewes had more type C and type D placentomes and fewer type B placentomes than their well-fed counterparts on day 135 (P,0·05). These changes were accompanied by higher IGFBP-6 mRNA expression in the maternal placental villi in undernourished ewes (P,0·05). The change in shape from a type A to a type C placentome was accompanied by flattening of the placentome and a reduction in the ratio of the area of unattached fetal allantochorion to interdigitated maternal and fetal villi. Within the intercotyledonary endometrium, expression of IGFBPs-3 and -5 mRNA in the glandular epithelium increased between days 45 and 90, showing an opposite trend with time to that found in the adjacent placentomes. This indicates tissue-specific control of IGFBP expression. In conclusion, this study has shown clear time-related changes in the uterine IGFBP system during pregnancy, which accompany changes in placental growth. Altered IGFBP expression may play a role in determining placental size in relation to nutritional status, but is unlikely to be the only mediator.

No abstract

In the placenta, cortisol is inactivated by NADP 1 -and NAD 1 -dependent isoforms of 11b-hydroxysteroid dehydrogenase (11bHSD). Decreased placental 11bHSD activities have been implicated in intrauterine growth restriction (IUGR) and fetal programming of adult diseases. The objective of this study was to investigate whether placental 11bHSD activities and fetal plasma cortisol:cortisone ratios could be affected by nutritional restriction of ewes (70% maintenance diet) throughout gestation, for specific stages of gestation, or prior to mating. Chronic nutritional restriction from day 26 of gestation onwards decreased NAD 1 -dependent 11bHSD activities by 52 6 4% and 45 6 6% on days 90 and 135 of gestation respectively.Although the decreases in enzyme activities were associated with fetal IUGR, the cortisol:cortisone ratio in fetal plasma was unaffected by chronic nutritional restriction throughout pregnancy. Nutritional restriction confined to early (days 26-45), mid-(days 46 -90) and late gestation (days 91-135), or the 30 days prior to mating, had no significant effect on NAD 1 -dependent, placental 11bHSD activities, nor was there evidence of IUGR. However, nutritional restriction at each stage of pregnancy and prior to mating was associated with significant decreases in the fetal plasma cortisol:cortisone ratio (3.2 6 0.7 in control fetuses; 1.0 to 1.6 in fetuses carried by nutritionally restricted ewes). We conclude that nutritional restriction of pregnant ewes for more than 45 consecutive days can significantly decrease NAD 1 -dependent placental 11bHSD activities in association with IUGR. While the cortisol:cortisone ratio in fetal plasma is sensitive to relatively acute restriction of nutrient intake, even prior to mating, this ratio does not reflect direct ex vivo measurements of placental 11bHSD activities.

No abstract