The epithelial Na+ channel (ENaC) in the female reproductive system: functions and regulatory factors

Abstract

Accumulated studies have shown that the epithelial Na⁺ channel (ENaC), a major Na⁺ channel for electrolyte and water homeostasis, is expressed in the female reproductive system and required for multiple key reproductive events. In tight epithelium of the uterus and cervix, hormonally regulated ENaC activity, together with other epithelial ion channels/transporters, shapes luminal fluid to support sperm transport, fertilization and embryo implantation. In the endometrium, apical ENaC in luminal epithelium senses embryo‑derived signals and couples them to signaling required for decidualization. In late pregnancy, ENaC in decidua and placenta contributes to pro‑inflammatory signaling and uterine contractions at labor. In non-epithelial granulosa cells in the ovary, ENaC modulates gonadotrophin signaling and estrogen production. Clinical and experimental evidence associate ENaC abnormalities with implantation failure, pregnancy loss, preterm labor and preeclampsia. This review summarizes these roles and discusses the potential of ENaC as diagnostic and therapeutic targets.