title: Leptin down-regulates γ-ENaC expression: a novel mechanism involved in low endometrial receptivity.
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.
  
  
  METHODS
  Controlled, prospective, clinical, experimental study.
  
  
  METHODS
  University-based infertility center.
  
  
  METHODS
  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.
  
  
  METHODS
  Human endometrial biopsies.
  
  
  METHODS
  Expression of ENaC mRNA and protein in endometrium.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, People's Republic of China; Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Xian-Hua
authors.initials: XH
authors.lastname: Lin
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, People's Republic of China; Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Miao-E
authors.initials: ME
authors.lastname: Liu
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, People's Republic of China; Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Xu
authors.affiliation: Medical Reproductive Center, Enze Maternity Hospital, Taizhou, Zhejiang, People's Republic of China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Chen
authors.affiliation: Medical Reproductive Center, Hangzhou First People's Hospital, Hangzhou, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, People's Republic of China; Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Shen
authors.initials: S
authors.lastname: Tian
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, People's Republic of China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.affiliation: Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, People's Republic of China; International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University, Hangzhou, People's Republic of China. Electronic address: huanghefg@hotmail.com.
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D000328:Adult; D015536:Down-Regulation; D004717:Endometrium / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000150:complications / Q000378:metabolism*; D020738:Leptin / Q000097:blood*; D050177:Overweight / Q000150:complications / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000097:blood*
chemical_list: D053503:Epithelial Sodium Channels; D020738:Leptin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: PCOS; attachment rate; endometrial receptivity; leptin; γ-ENaC