Scope: Uterine receptivity is a major restriction of embryo implantation and survival, and the endometrial luminal epithelium serves as the transient gateway for uterine receptivity and embryo implantation. Butyrate is reported to promote the success of embryo implantation, but the effects and mechanism of butyrate on uterine receptivity are still unknown.
Methods and results: Porcine endometrial epithelial cells (PEECs) are used as a model, and the cellular receptivity changes, metabolism, and gene expression profiles influenced by butyrate are analyzed. The study finds that butyrate improves receptive changes in PEECs, including inhibiting proliferation, exhibiting more pinocytosis on the cell surface, and increasing adhesiveness to porcine trophoblast cells. In addition, butyrate increases prostaglandin synthesis and markedly impacts purine metabolism, pyrimidine metabolism, and the FoxO signaling pathway. siRNA to inhibit the expression of FoxO1 and chromatin immunoprecipitation-sequencing (ChIP-seq) of H3K9ac are used to demonstrate that the H3K9ac/FoxO1/PCNA pathway can contribute to the effects of cell proliferation inhibition and uterine receptivity improvement induced by butyrate.
Conclusion: The findings reveal that butyrate improves endometrial epithelial cell receptivity by enhancing the acetylation of histone H3K9, which shows nutritional regulation and therapeutic potential for poor uterine receptivity and difficulty in embryo implantation.
Keywords: H3K9ac; butyrate; cell proliferation; endometrial epithelial cells; uterine receptivity.
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