The effect of maternal undernutrition on the placental growth trajectory and the uterine insulin-like growth factor axis in the pregnant ewe

Abstract

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.

Effect of Morphology on Placentome Size, Vascularity, and Vasoreactivity in Late Pregnant Sheep1

“…These data are similar to results for control ewes in studies by Vatnick et al [4], Clarke et al [13], Steyn et al [14], Gardner et al [15], and Osgerby et al [16], as well as for ewes in which the fetal or placental weights were compromised [5,[13][14][15][16][17][18][19][20][21].…”

The IGF Axis in Baboon Pregnancy: Placental and Systemic Responses to Feeding 70% Global Ad Libitum Diet

“…In sheep, mild and moderate maternal NR (30-50%) during early gestation (the period of maximal placental growth and the time comparable to the maternal NR period in our study) induced no decrease in fetal body weight, consistent with our findings [26]. As in our study, Osgerby et al [27] detected no differences in placental weight when ewes were exposed to 30% maternal NR during the first half of gestation. Overall, fetal growth is a very poor measure of altered fetal organ development and it is now clear that considerable functional and structural changes can take place in the placenta and fetal organs in the absence of any gross weight change.…”

Effect of nutrient restriction on the somatotropes and substance P-immunoreactive cells in the pituitary of the female ovine fetus

“…It is also that although nutritional restriction for 10 days in utero did not affect the birth weight of the ovine fetus, the hypothalamo-pituitaryadrenal axis was significantly altered in the adult [35]. Similarly, a 30% reduction in nutrients from Day 26 of gestation in the ewe until Days 45, 90, or 135, did not decrease total body weight but a reduction in several organ weights was noted [36]. Maternal insults, which have little, or no, effect on birth weight, can also alter glucose tolerance, blood pressure, and hypothalamopituitary adrenal function [3].…”

“…Increased GH secretion could alter fetal metabolic regulation [34], resulting in a normal body weight. There is also evidence that gestational nutrient restriction can alter the metabolism of fuels causing vital organs to remain at almost a normal weight at the expense of non-vital tissues [35,36]. Nutrients may be shunted from growth promoting processes (via IGFs) to vital processes [37][38][39].…”