The Balance of [Formula: see text] Secretion vs. Reabsorption in the Endometrial Epithelium Regulates Uterine Fluid...

Uterine fluid contains a high concentration of [Formula: see text] which plays an essential role in sperm capacitation and fertilization. In addition, the [Formula: see text] concentration in uterine fluid changes periodically during the estrous cycle. It is well-known that the endometrial epithelium contains machineries involving the apical SLC26 family anion exchangers for secreting [Formula: see text] into the uterine fluid. In the present study, we find for the first time that the electroneutral Na⁺/[Formula: see text] cotransporter NBCn1 is expressed at the apical membrane of the endometrial epithelium. The protein abundance of the apical NBCn1 and that of the apical SLC26A4 and SLC26A6 are reciprocally regulated during the estrous cycle in the uterus. NBCn1 is most abundant at diestrus, whereas SLC26A4/A6 are most abundant at proestrus/estrus. In the ovariectomized mice, the expression of uterine NBCn1 is inhibited by β-estradiol, but stimulated by progesterone, whereas that of uterine SLC26A4/A6 is stimulated by β-estradiol. In vivo perfusion studies show that the endometrial epithelium is capable of both secreting and reabsorbing [Formula: see text]. Moreover, the activity for [Formula: see text] secretion by the endometrial epithelium is significantly higher at estrus than it is at diestrus. The opposite is true for [Formula: see text] reabsorption. We conclude that the endometrial epithelium simultaneously contains the activity for [Formula: see text] secretion involving the apical SLC26A4/A6 and the activity for [Formula: see text] reabsorption involving the apical NBCn1, and that the acid-base homeostasis in the uterine fluid is regulated by the finely-tuned balance of the two activities.