Department of Pharmacology & Therapeutics, McGill University, Montreal, QC H4A 3J1, Canada.
Department of Pediatrics, Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada.
Int J Mol Sci. 2022 Apr 29;23(9):4978. doi: 10.3390/ijms23094978.
Group B (GBS) is a leading cause of placental infection, termed chorioamnionitis. Chorioamnionitis is associated with an increased risk of neurobehavioral impairments, such as autism spectrum disorders, which are more prominent in males than in female offspring. In a pre-clinical model of chorioamnionitis, a greater inflammatory response was observed in placenta associated with male rather than female fetuses, correlating with the severity of subsequent neurobehavioral impairments. The reason for this sex difference is not understood. Our hypothesis is that androgens upregulate the placental innate immune response in male fetuses. Lewis dams were injected daily from gestational day (G) 18 to 21 with corn oil (vehicle) or an androgen receptor antagonist (flutamide). On G 19, dams were injected with saline (control) or GBS. Maternal, fetal sera and placentas were collected for protein assays and in situ analyses. Our results showed that while flutamide alone had no effect, a decrease in placental concentration of pro-inflammatory cytokines and infiltration of polymorphonuclear cells was observed in flutamide/infected compared to vehicle/infected groups. These results show that androgens upregulate the placental innate immune response and thus may contribute to the skewed sex ratio towards males observed in several developmental impairments resulting from perinatal infection/inflammation.
B 组链球菌（GBS）是导致胎盘感染的主要原因，被称为绒毛膜羊膜炎。绒毛膜羊膜炎与神经行为障碍风险增加有关，例如自闭症谱系障碍，其在男性后代中比女性后代更为明显。在绒毛膜羊膜炎的临床前模型中，与女性胎儿相比，男性胎儿的胎盘与炎症反应更为明显，这与随后神经行为障碍的严重程度相关。造成这种性别差异的原因尚不清楚。我们的假设是雄激素使男性胎儿的胎盘固有免疫反应上调。妊娠第 18 天至 21 天，Lewis 孕鼠每天接受玉米油（载体）或雄激素受体拮抗剂（氟他胺）注射。在第 19 天，孕鼠接受生理盐水（对照）或 GBS 注射。收集母体、胎儿血清和胎盘进行蛋白分析和原位分析。结果表明，虽然氟他胺单独使用没有效果，但与载体/感染组相比，氟他胺/感染组胎盘促炎细胞因子浓度降低，多形核细胞浸润减少。这些结果表明，雄激素使胎盘固有免疫反应上调，因此可能导致围产期感染/炎症引起的几种发育障碍中男性比例偏斜。
