Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Uterine kisspeptin receptor critically regulates epithelial estrogen receptor α transcriptional activity at the time of embryo implantation in a mouse model.

Authors: Schaefer, Jennifer; Vilos, Angelos G; Vilos, George A; Bhattacharya, Moshmi; Babwah, Andy V

Published In Mol Hum Reprod, (2021 Sep 29)

Abstract: Embryo implantation failure is a major cause of infertility in women of reproductive age and a better understanding of uterine factors that regulate implantation is required for developing effective treatments for female infertility. This study investigated the role of the uterine kisspeptin receptor (KISS1R) in the molecular regulation of implantation in a mouse model. To conduct this study, a conditional uterine knockout (KO) of Kiss1r was created using the Pgr-Cre (progesterone receptor-CRE recombinase) driver. Reproductive profiling revealed that while KO females exhibited normal ovarian function and mated successfully to stud males, they exhibited significantly fewer implantation sites, reduced litter size and increased neonatal mortality demonstrating that uterine KISS1R is required for embryo implantation and a healthy pregnancy. Strikingly, in the uterus of Kiss1r KO mice on day 4 (D4) of pregnancy, the day of embryo implantation, KO females exhibited aberrantly elevated epithelial ERα (estrogen receptor α) transcriptional activity. This led to the temporal misexpression of several epithelial genes [Cftr (Cystic fibrosis transmembrane conductance regulator), Aqp5 (aquaporin 5), Aqp8 (aquaporin 8) and Cldn7 (claudin 7)] that mediate luminal fluid secretion and luminal opening. As a result, on D4 of pregnancy, the lumen remained open disrupting the final acquisition of endometrial receptivity and likely accounting for the reduction in implantation events. Our data clearly show that uterine KISS1R negatively regulates ERα signaling at the time of implantation, in part by inhibiting ERα overexpression and preventing detrimentally high ERα activity. To date, there are no reports on the regulation of ERα by KISS1R; therefore, this study has uncovered an important and powerful regulator of uterine ERα during early pregnancy.

PubMed ID: 34524460 Exiting the NIEHS site

MeSH Terms: Animals; Aquaporin 5/genetics; Aquaporin 5/metabolism; Aquaporins/genetics; Aquaporins/metabolism; Claudins/genetics; Claudins/metabolism; Cystic Fibrosis Transmembrane Conductance Regulator/genetics; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism; Embryo Implantation*; Epithelial Cells/metabolism*; Estrogen Receptor alpha/genetics; Estrogen Receptor alpha/metabolism*; Female; Gene Expression Regulation, Developmental*; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Pregnancy; Receptors, Kisspeptin-1/genetics; Receptors, Kisspeptin-1/metabolism*; Signal Transduction; Time Factors; Transcription, Genetic*; Uterus/metabolism*

Back
to Top