Sexually dimorphic crosstalk at the maternal-fetal interface

The first trimester is a critical window of maternal-fetal communication for pregnancy. Using single cell RNA-sequencing to dissect placenta heterogeneity, we identified five major cell types (trophoblasts, stromal cells, hofbauer cells, antigen presenting cells and endothelial cells). We identified seven unique trophoblast subclusters, including new subtypes that transition into the terminal cell types, extra-villous trophoblasts and syncytiotrophoblasts. As fetal sex impacts pregnancy, we analyzed sex differences in each cell type and identified differences in immune cell function. TGFβ1, β-estradiol, and dihydrotestosterone emerge as upstream regulators of sexually dimorphic genes in a cell type specific manner. Thus, the fetal contribution at the maternal-fetal interface is cell and sex specific. Examination of transcriptomic profiles at the single cell level in the primary tissues from first trimester human placenta. In total, 6 placental tissues were utilized, of which 3 were from female conceptions and 3 were from male conceptions.

妊娠早期（first trimester）是妊娠过程中母胎通信的关键窗口期。本研究借助单细胞RNA测序（single cell RNA-sequencing）解析胎盘异质性，鉴定出5种主要细胞类型：滋养层细胞（trophoblasts）、基质细胞（stromal cells）、霍夫鲍尔细胞（hofbauer cells）、抗原呈递细胞（antigen presenting cells）及内皮细胞（endothelial cells）。我们进一步鉴定出7个独特的滋养层细胞亚簇，包含可向终末细胞类型分化的新型亚类——绒毛外滋养层细胞（extra-villous trophoblasts）与合体滋养层细胞（syncytiotrophoblasts）。鉴于胎儿性别可影响妊娠进程，我们对每种细胞类型的性别差异展开分析，并鉴定出免疫细胞功能层面的差异。转化生长因子β1（TGFβ1）、β-雌二醇（β-estradiol）及二氢睾酮（dihydrotestosterone）以细胞类型特异性的方式，被鉴定为性别二态性基因的上游调控因子。由此可见，母胎界面的胎儿贡献具有细胞类型与性别特异性。本数据集针对妊娠早期人胎盘原代组织的单细胞转录组谱展开分析，共纳入6份胎盘组织样本，其中3份来自女性胎儿妊娠，3份来自男性胎儿妊娠。