Centre for Trophoblast Research - Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Front Endocrinol (Lausanne). 2023 Feb 10;14:1116770. doi: 10.3389/fendo.2023.1116770. eCollection 2023.
Conditions such as small for gestational age (SGA), which is defined as birthweight less than 10 percentile for gestational age can predispose to neurodevelopmental abnormalities compared to babies with normal birthweight. Fetal growth and birthweight depend on placental function, as this organ transports substrates to the developing fetus and it acts as a source of endocrine factors, including steroids and prolactins that are required for fetal development and pregnancy maintenance. To advance our knowledge on the aetiology of fetal growth disorders, the vast majority of the research has been focused on studying the transport function of the placenta, leaving practically unexplored the contribution of placental hormones in the regulation of fetal growth. Here, using mice and natural variability in fetal growth within the litter, we compared fetuses that fell on or below the 10 percentile (classified as SGA) with those that had adequate weight for their gestational age (AGA). In particular, we compared placental endocrine metabolism and hormone production, as well as fetal brain weight and expression of developmental, growth and metabolic genes between SGA and AGA fetuses. We found that compared to AGA fetuses, SGA fetuses had lower placental efficiency and reduced capacity for placental production of hormones (e.g. steroidogenic gene , prolactin , and pregnancy-specific glycoproteins ). Brain weight was reduced in SGA fetuses, although this was proportional to the reduction in overall fetal size. The expression of glucose transporter 3 () was reduced despite the abundance of AKT, FOXO and ERK proteins were similar. Developmental ( and ) and microglia genes (), as well as the pregnancy-specific glycoprotein receptor ( were lower in the brain of SGA versus AGA fetuses. In this mouse model of SGA, our results therefore demonstrate that placental endocrine dysfunction is associated with changes in fetal growth and fetal brain development.
与正常出生体重的婴儿相比，胎龄小（SGA）等情况会导致神经发育异常，SGA 是指出生体重低于胎龄第 10 百分位。胎儿的生长和出生体重取决于胎盘的功能，因为该器官将底物输送到发育中的胎儿，并作为包括类固醇和催乳素在内的内分泌因子的来源，这些因子是胎儿发育和妊娠维持所必需的。为了深入了解胎儿生长障碍的病因，绝大多数研究都集中在研究胎盘的转运功能上，而实际上尚未探索胎盘激素在调节胎儿生长中的作用。在这里，我们使用小鼠和胎内生长的自然变异性，比较了处于第 10 百分位以下（归类为 SGA）的胎儿与具有适当胎龄体重的胎儿（AGA）。特别是，我们比较了 SGA 和 AGA 胎儿之间胎盘内分泌代谢和激素产生以及胎儿大脑重量和发育、生长和代谢基因的表达。我们发现，与 AGA 胎儿相比，SGA 胎儿的胎盘效率较低，胎盘产生激素的能力降低（例如，类固醇生成基因、催乳素和妊娠特异性糖蛋白）。SGA 胎儿的大脑重量降低，但这与整体胎儿大小的减少成比例。尽管 AKT、FOXO 和 ERK 蛋白的丰度相似，但葡萄糖转运蛋白 3 () 的表达减少。发育（和）和小胶质细胞基因（）以及妊娠特异性糖蛋白受体（在 SGA 与 AGA 胎儿的大脑中的表达较低。因此，在 SGA 的这种小鼠模型中，我们的研究结果表明，胎盘内分泌功能障碍与胎儿生长和胎儿大脑发育的变化有关。
