Expression and Hormonal Regulation of Entpd3 at Various Estrous Cycle Stages in the Mouse Uterus

Ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3), a plasma membrane-bound metabolic enzyme, converts extracellular nucleotides into nucleosides. ENTPD3 is involved in various pathophysiological processes, including cellular adhesion, metabolism, activation, and migration. However, its specific function in the uterus remains unclear. This study aimed to investigate the expression pattern and localization of Entpd3 in the mouse uterus throughout the estrous cycle using immunohistochemistry (IHC), quantitative real-time PCR, and western blot analysis. The effect of sex steroid hormones on Entpd3 expression was also examined in ovariectomized (OVX) mice treated with 17β-estradiol (E2)/progesterone (P4) and estrogen receptor antagonist (Fulvestrant)/progesterone receptor antagonist (Mifepristone). Results demonstrated that elevated levels of Entpd3 mRNA and protein were noted during estrus and metestrus, with a decline in diestrus and proestrus. IHC revealed abundant ENTPD3 in the cytoplasm of glandular and luminal epithelial cells during estrus and metestrus. Additionally, treatment with E2 or P4 in OVX mice downregulated the expression of Entpd3 in the mouse uterus, which was rescued by Fulvestrant or Mifepristone. This study demonstrated that the expression of Entpd3 in the mouse uterus varied dynamically throughout the estrous cycle and was steroid-dependent, suggesting a potential role for Entpd3 in female mice's reproductive function.