Uterine epithelial ERα regulates preimplantation uterine luminal epithelial and uterine mRNAs

Uterine epithelial estrogen receptor α (ERα) deficiency in epiERα-/- (Esr1f/-Wnt7aCre/+) mice leads to dysregulated environment of uterine lumen, which is lined by uterine luminal epithelium (LE). We hypothesized that transcriptomes in the LE layer held molecular keys to understanding ERα in regulating preimplantation uterine environment. Day 0.5 post-coitum (D0.5) and D3.5 LE layer (isolated via enzymatic digestion), digested uterus (DU), and uterus (U) from Esr1f/- (control) and epiERα-/- mice were processed for mRNA-seq. There were minimal differentially expressed genes (DEGs: transcripts per million > 1, fold-change > 2, false discovery rate < 0.05) between DU and U. Between D0.5 and D3.5 Esr1f/- LE layer, the top upregulated and downregulated gene ontology biological process (GOBP) pathways were on cellular processes and innate immune responses, respectively. Compared to Esr1f/- LE layer, the most upregulated and downregulated pathways in D0.5 epiERα-/- LE layer were on innate immune responses and on biosynthesis and metabolism, respectively; while those in D3.5 epiERα-/- LE layer were on cell division and on signaling and metabolic processes, respectively. Na+ transmembrane transport was among shared upregulated pathways in D0.5 and D3.5 epiERα-/- LE layer. Between Esr1f/- and epiERα-/-, most DEGs in U were also DEGs in the LE layer, and limited DEGs in U only with higher expression than in the LE layer were related to immune responses, implying potential paracrine effects of uterine epithelial ERα. Selected DEGs were verified by realtime PCR and immunohistochemistry. This mRNA-seq dataset provides molecular keys to understanding temporal (e.g., innate immunity) and constituent (e.g., uterine fluid movement) functions, and potential paracrine effects of uterine epithelial ERα in regulating the preimplantation uterine environment.