Endometrial zinc transporter Slc39a10/Zip10 is indispensable for progesterone responsiveness and successful pregnancy in mice

Abstract

Zinc is a critical trace element that is important for various biological functions including male and female reproductive systems, but the molecular mechanisms that underlie fertility have been unclear. We show here for the first time that zinc signaling in the endometrial tissue is indispensable for successful embryo implantation in mice. We observed that a uterine-specific genetic deletion of Slc39a10/Zip10, which encodes one of the zinc transporters to elevate the cytoplasmic level of zinc, results in severe female infertility due to failure of embryo invasion into the endometrium. Zip10 mRNA is expressed in uterine tissues, especially in the decidualizing stromal cells during embryo implantation. Absence of Zip10 results in the suppression of zinc ion influx in the uterine stromal cells and an attenuation of progesterone - progesterone receptor signals between the epithelium and the stroma, leading to failure of embryo invasion due to sustained epithelial integrity and subsequent embryonic loss. Our findings (i) highlight a biological relevance of ZIP10-mediated zinc homeostatic regulation in the establishment of a successful pregnancy and (ii) will help to prevent infertility in humans.