The gasotransmitter hydrogen sulfide inhibits transepithelial anion secretion of pregnant mouse endometrial epithelium.

Endometrial epithelium exhibits a robust ion transport activity required for dynamical regulation of uterine fluid environment and thus embryo implantation. However, there still lacks a thorough understanding of the ion transport processes and regulatory mechanism in peri-implantation endometrial epithelium. As a gaseous signaling molecule or gasotransmitter, hydrogen sulfide (HS) regulates a myriad of cellular and physiological processes in various tissues, including the modulation of ion transport proteins in epithelium. This study aimed to investigate the effects of HS on ion transport across mouse endometrial epithelium and its possible role in embryo implantation. The existence of endogenous HS in pregnant mouse uterus was tested by the detection of two key HS-generating enzymes and measurement of HS production rate in tissue homogenates. Transepithelial ion transport processes were electrophysiologically assessed in Ussing chambers on early pregnant mouse endometrial epithelial layers, demonstrating that HS suppressed the anion secretion by blocking cystic fibrosis transmembrane conductance regulator (CFTR). HS increased intracellular Cl concentration ([Cl]) in mouse endometrial epithelial cells, which was abolished by pretreatment with the CFTR selective inhibitor CFTR-172. The cAMP level in mouse endometrial epithelial cells was not affected by HS, indicating that HS blocked CFTR in a cAMP-independent way. In vivo study showed that interference with HS synthesis impaired embryo implantation. In conclusion, our study demonstrated that HS inhibits the transepithelial anion secretion of early pregnant mouse endometrial epithelium via blockade of CFTR, contributing to the preparation for embryo implantation.