Ion Channels as Gatekeepers of Fertility: from Uterine Kir7.1 to Sperm CatSper.

Abstract

Ion channels coordinate diverse physiological functions through tightly regulated fluxes of Ca²⁺, K⁺, Na⁺, Cl^-, and H⁺ across both plasma and intracellular membranes. In the reproductive system, ion channels have emerged as key regulators of processes essential for reproductive success. They control epithelial transport and ciliary activity in the oviduct, regulate uterine smooth muscle contractility and receptivity, and orchestrate sperm capacitation, hyperactivation, acrosome reaction, and fertilization. These functions require precise spatial and temporal integration of environmental cues, including bioactive lipids, pH, temperature, and mechanical forces encountered throughout the reproductive tract. Dysregulation of ion channel activity has been increasingly linked to infertility, pregnancy complications, and other reproductive disorders. Recent advances in live-cell imaging, superresolution microscopy, electrophysiology, and cryo-electron microscopy have transformed our understanding of ion channel architecture, regulation, and organization within specialized membrane microdomains in reproductive tissues. In this review, we highlight recent discoveries of ion channels and their regulatory mechanisms specifically in reproductive tissues, with a focus on emerging roles of potassium channel Kir7.1 in uterine physiology and calcium channel CatSper in sperm motility, and discuss emerging questions that will guide future research in reproductive ion channel biology.