Osgerby J C, Wathes D C, Howard D, Gadd T S
Reproduction and Development Group, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts AL9 7TA, United Kingdom.
J Endocrinol. 2004 Jul;182(1):89-103. doi: 10.1677/joe.0.1820089.
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.
胎盘是一个高效的多功能器官，介导母体与胎儿之间营养物质、气体和代谢废物的交换。本研究调查了妊娠45天、90天和135天时，母体长期营养不足（估计需求量的70%）对母羊胎盘生长轨迹的影响。使用原位杂交分析研究胰岛素样生长因子（IGF）系统，以确定营养介导的胎盘生长改变是否通过胎盘IGF表达的改变来调节。胎盘重量在45天至90天之间增加（P<0.01），同时母体胎盘小叶中IGF结合蛋白（IGFBP）-3、-5和-6的表达降低（P<0.05），尽管母体绒毛中IGF-II mRNA水平保持不变。胎盘小叶数量不受饮食或胎龄的影响。在100%维持日粮的母羊中，胎盘重量在90天至135天之间保持恒定，但在70%日粮的母羊中，在此期间胎盘重量下降（P<0.05）。大体形态也发生了改变，因此在135天时，营养不良的母羊比营养良好的母羊有更多的C型和D型胎盘小叶，而B型胎盘小叶更少（P<0.05）。这些变化伴随着营养不良母羊母体胎盘绒毛中IGFBP-6 mRNA表达升高（P<0.05）。从A型胎盘小叶到C型胎盘小叶的形状变化伴随着胎盘小叶变平以及未附着的胎儿尿囊绒毛与交错的母体和胎儿绒毛面积比降低。在子叶间子宫内膜中，腺上皮中IGFBP-3和-5 mRNA的表达在45天至90天之间增加，显示出与相邻胎盘小叶中发现的时间趋势相反。这表明IGFBP表达存在组织特异性控制。总之，本研究表明孕期子宫IGFBP系统存在明显的时间相关变化，这些变化伴随着胎盘生长的变化。IGFBP表达的改变可能在决定与营养状况相关的胎盘大小方面起作用，但不太可能是唯一的调节因子。
