Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
Reprod Sci. 2023 Jun;30(6):1994-1997. doi: 10.1007/s43032-022-01157-w. Epub 2022 Dec 27.
Gestational hypoxia is a major contributor to fetal growth restriction (FGR) and perinatal morbidity and mortality and has been closely linked to the activation of the unfolded protein response (UPR) in the placenta. Recent studies on adverse pregnancy conditions show differential adaptive responses in pregnancies carrying male or female fetuses. Here, we use an established rat model of hypoxic pregnancy and FGR to test the hypothesis that chronic hypoxia promotes sexually dimorphic activation of the placental UPR. Our data showed that gestational hypoxia increased glucose regulatory protein 78 (GRP78) expression in male placentae, increased activating transcription factor 6 activation (ATF6) in female placentae, and did not induce changes in other UPR markers. In addition, gestational hypoxia reduced fetal weight only in males and ATF6 activation correlated with an increase in the fetal crown-rump-length/body weight ratio only in females. These results suggest sex-specific divergence in the placental adaptive response to gestational hypoxia, which may account for the sexual dimorphism observed in placental function and pregnancy outcomes in complicated pregnancies.
妊娠缺氧是胎儿生长受限（FGR）和围产期发病率和死亡率的主要原因，并且与胎盘未折叠蛋白反应（UPR）的激活密切相关。最近对不良妊娠情况的研究表明，携带男性或女性胎儿的妊娠存在不同的适应性反应。在这里，我们使用已建立的缺氧妊娠和 FGR 大鼠模型来检验慢性缺氧促进胎盘 UPR 性别二态性激活的假设。我们的数据表明，妊娠缺氧增加了雄性胎盘中葡萄糖调节蛋白 78（GRP78）的表达，增加了雌性胎盘中激活转录因子 6 的激活（ATF6），但没有诱导其他 UPR 标志物的变化。此外，妊娠缺氧仅降低雄性胎儿的体重，而 ATF6 的激活与雌性胎儿的胎头-臀长/体重比增加相关。这些结果表明，胎盘对妊娠缺氧的适应性反应存在性别特异性差异，这可能解释了复杂妊娠中胎盘功能和妊娠结局观察到的性别二态性。
