Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enables Murine Embryo Implantation

Using conditional knockout technology, we demonstrate that steroid receptor coactivator-2 (SRC-2) is essential for development of the receptive uterus for embryo implantation. Through bulk RNA-seq analysis, we reveal that endometrial SRC-2 is required for not only the induction of the expression of established genes associated with uterine receptivity but also for the expression of genes involved in endometrial epithelial changes that enable attachment and invasion of the embryo into the underlying stroma. Together, these RNA-seq results underscore the importance of SRC-2 as a transcriptional coregulator in the endometrium during the periimplantation period. To investigate the SRC-2 gene signature in regulation of embryo implantation, the mouse gestation day 5 uterine tissue from 3 different SRC-2f/f and SRC-2d/d mice were used. Total RNA was isolated from control (SRC-2f/f) and mutant (SRC-2d/d) GD 5 uterus and subjected to the RNAseq assay.本研究利用条件性基因敲除（conditional knockout）技术，证实类固醇受体辅激活因子2（SRC-2）对胚胎着床所需的容受态子宫发育至关重要。通过批量RNA测序（bulk RNA-seq）分析，本研究揭示子宫内膜中的SRC-2不仅参与调控已确认的子宫容受相关基因的表达激活，还调控参与子宫内膜上皮细胞改变的基因表达——这些改变可使胚胎黏附并侵袭下方基质。综上，本次RNA测序结果凸显了着床窗口期子宫内膜中SRC-2作为转录辅调控因子的重要性。为探究调控胚胎着床的SRC-2基因表达特征，本研究采集了3只SRC-2f/f型与3只SRC-2d/d型小鼠的妊娠第5天子宫组织。本研究从对照组（SRC-2f/f）与突变组（SRC-2d/d）的妊娠第5天子宫中提取总RNA，并开展RNA测序实验。