The endometrial microbiome of clinical miscarriage, ectopic pregnancy and during early pregnancy in a successful live-birth

Abstract

RESULTS: 1301 RNA species were common to both the mouse and human DEGs. 318 of these genes were directly bound by FOXO1. Pathway analysis identified Wnt/B-catenin signaling (-log(p-value) 4.14, Z score -0.626), estrogen mediated proliferation (-log(p-value) 10, Z score -3.05), and IL-6 signaling (-log(p-value) 4.73, Z score 0.943) as significantly altered by both human cycle phase and murine FOXO1 deletion, strongly suggesting a role of FOXO1 in these critical pathways for normal endometrial function. ChIP-Seq demonstrated direct FOXO1 binding to multiple regulated genes involved in estrogen-mediated proliferation, IL-6 signaling, and Wnt/b-catenin signaling, supporting a direct action of FOXO1 on these essential signaling pathways. FOXO1 was also found to directly bind several upstream regulators critical to endometrial receptivity, including CEBPB and CCND1.CONCLUSIONS: Epithelial FOXO1 directly regulates key pathways necessary for human uterine receptivity.References: 1. Vasquez YM, Wang X, Wetendorf M, et al. FOXO1 regulates uterine epithelial integrity and progesterone receptor expression critical for embryo implantation.