Endometrial assembloid model reveals endometrial adenogenesis regulation by estradiol-driven WNT7B expression [bulk RNA-seq]

Little is known about the adenogenesis of human endometrial glands. This study explored endometrial adenogenesis using a novel three-dimensional endometrial assembloid model that integrates human endometrial organoids (EOs) and human endometrial stromal cells (HESCs). The model effectively recapitulated endometrial tubular gland formation, underscoring the critical role of stromal-epithelial interactions. Transcriptomic analyses identified WNT7B as a key intrinsic regulator for EO-derived tubular gland formation, which is extrinsically regulated by TGFβ1-VDR interaction between HESCs and EOs. Estradiol stimulated endometrial gland development via WNT7B downregulation in EOs. This finding was validated in an estradiol-stimulated mouse model and clinical samples from women undergoing in vitro fertilization (IVF) cycles. Uterine-specific WNT7B knockout in mice further confirmed its inhibitory role in endometrial gland development. This study offers insights into endometrial adenogenesis and potential therapeutic targets for related endometrial disorders. As differential tubular gland development ability has been identified in different endometrial organoid samples, we tried to identify the differential gene expression patterns in EOs with and without tubular gland development capacity. EOs were collected separately that with and without tube development potential for RNA sequencing analysis.