Leptin downregulates γENaC expression A novel mechanism involved in low endometrial receptivity

Capsule:
Polycystic ovary syndrome patients who are overweight or obese showed increased serum leptin levels. High leptin levels may reduce g-epithelial Naþ channel expression in human endometrium via activating the STAT3 pathway, resulting in attenuated endometrial receptivity.

Authors:
Xian-Hua Lin, M.D., Miao-E. Liu, M.B., Hai-Yan Xu, M.B., Xue-Jun Chen, M.D., Hui Wang, M.B., Shen Tian, M.D., Jian-Zhong Sheng, Ph.D., He-Feng Huang, M.D.

Volume 103, Issue 1, Pages 228-235

Abstract:

Objective:
To examine epithelial Na+ channel (ENaC) expression in endometrium of overweight/obese women with polycystic ovary syndrome (PCOS) during the window of implantation, and to explore the mechanism linking leptin-mediated reduction of γ-ENaC to low endometrial receptivity.

Design:
Controlled, prospective, clinical, experimental study.

Setting:
University-based infertility center.

Patient(s):
Blood and endometrium samples were collected from 12 control women and 12 overweight/obese PCOS patients. Pregnancy outcomes were obtained from 245 women with male-factor infertility (533 cycles) and 57 infertile women with PCOS (120 cycles) who underwent intrauterine insemination.

Intervention(s):
Human endometrial biopsies.

Main Outcome Measure(s):
Expression of ENaC mRNA and protein in endometrium.

Result(s):
The expression of γ-ENaC decreased in the secretory phase endometrium of PCOS patients who showed increased serum leptin levels. In cultured endometrial cells (Ishikawa cells), leptin dose-dependently down-regulated the expression of γ-ENaC and reduced the JAr spheroid attachment rate, which could be blocked by knockdown of STAT3, a signal in the pathway of leptin receptor activation. The overweight/obese PCOS patients with increased serum leptin levels showed a significantly increased biochemical pregnancy rate, suggesting that high leptin might attenuate endometrial receptivity and increase very early pregnancy loss.

Conclusion(s):
High serum leptin may reduce endometrial receptivity by activating the STAT3 signal pathway and down-regulating γ-ENaC expression in the endometrium. These results provide valuable new insights into the molecular mechanisms linking abnormal ENaC gene expression to early pregnancy loss in overweight/obese PCOS patients.

Translate »