Mechanism of human chorionic gonadotropin in endometrial receptivity via the miR‐126‐3p/PI3K/Akt/eNOS axis

Abstract

Human chorionic gonadotropin (hCG) might affect endometrial receptivity, exerting integral roles in embryo implantation. This study explored the action of hCG in endometrial receptivity via the miR-126-3p/PIK3R2/PI3K/Akt/eNOS axis. The embryo implantation dysfunction (EID) mouse models were established by administrating mifepristone and human endometrial epithelial cells (EECs) were used for in vivo experiments, both followed by hCG treatment. Expression level of CD105 and protein levels of cadherin CD144 and CD146 in mice were determined by immunohistochemistry and Western blot. The levels of miR-126-3p and PIK3R2 mRNA and PIK3R2, p-PI3K p85 α, PI3K p110 α, p-Akt, Akt, p-eNOS, and eNOS protein levels were measured. Cell proliferation was evaluated by CCK-8 and EdU assays. The binding sites of miR-126-3p and PIK3R2 were predicted and verified. hCG-treated EECs were further transfected with miR-126-inhibitor for functional rescue experiments. hCG ameliorated endometrial receptivity in EID mice. Moreover, hCG promoted miR-126-3p and suppressed PIK3R2 in EID mice and EECs. miR-126-3p targeted PIK3R2. EEC proliferation was enhanced after hCG treatment but inhibited by miR-126-3p downregulation. Both in vivo and in vitro experiments validated that hCG activated the PI3K/Akt/eNOS pathway through the miR-126-3p/PIK3R2 axis. Collectively, hCG improves endometrial receptivity by activating the PI3K/Akt/eNOS pathway via regulating miR-126-3p/PIK3R2.

Comparison of microbial abundance and diversity in uterine and peritoneal fluid in infertile patients with or without endometriosis

“…The Insulin signaling pathway, NOD-like receptor signaling pathway, and PI3K-Akt signaling pathway were all downregulated in patients with stage III-IV EM. NOD-like receptor Pyrins-3 (NLRP3) upregulation can help in endometrial conditioning for embryo implantation [ 32 , 33 ], while Insulin signaling is vital for decidualization, a key pregnancy process [ 34 ]. Our data suggest that EM might impact fertility by altering uterine microbiota, potentially affecting receptivity.…”