Decoy receptor 3 expression during the menstrual cycle and pregnancy, and regulation by sex steroids in endometrial cells in vitro

Abstract

Background: Decoy receptor 3 (DcR3) is a soluble receptor belonging to the tumor necrosis factor receptor superfamily and can inhibit Fas ligand-induced apoptosis. DcR3 is related to carcinogenesis, but is found in human gestational tissues, where the function is uncertain. We aimed to determine DcR3 expression and regulation in endometrial cells in vitro, and throughout the menstrual cycle and pregnancy in vivo. Methods: Serum DcR3 levels were measured at various stages of the menstrual cycle (n = 40 women) and pregnancy (n = 20). DcR3 transcript and protein levels were analyzed in RL95-2 endometrial cells after treatment with estradiol (E2) (± anti-estrogen) and/or progesterone (± anti-progesterone). Finally, DcR3 protein and transcript were examined in decidua and chorionic villi from normal (n = 14) and anembryonic (n = 14) pregnancies. Results: We identified a trend towards cyclic changes of serum DcR3 levels in the normal menstrual cycle, peaking at the mid-luteal phase, and relatively lower, more stable serum levels throughout normal gestation. DcR3 protein levels were higher in decidua than chorionic villi in normal pregnancy (P = 0.001), and levels in decidua were significantly lower in anembryonic than in normal pregnancies (P = 0.034). Physiologic concentrations of E2 and/or progesterone stimulated DcR3 transcripts in RL95-2 endometrial cells. Conclusions: This study suggested that DcR3 expression varies during the menstrual cycle and is regulated by sex steroid hormones in vitro in endometrial cells. Human gestational tissues showed a differential production of DcR3, and decidual DcR3 protein was lower in anembryonic than normal pregnancies, suggesting an active role of DcR3 in the regulation of successful pregnancies.