Progesterone Receptors Signaling and Upregulation of Decay-Accelerating Factor (DAF/CD55)

INTRODUCTION: Decay-accelerating factor (DAF/CD55) functions to prevent autologous-complement-mediated tissue damage. Our previous data indicate that CD55 expression is reduced in patients exhibiting luteal phase defects and endometriosis, both of which can lead to infertility. Progesterone is often used for successful treatment of these conditions. The understanding of this therapeutic mechanism would improve the treatment of infertility. We investigate the hypothesis that progesterone induces decay-accelerating factor expression in endometrial cells by signaling progesterone receptors. METHODS: We treated ECC1 cells with estrogen (16 ng/mL) and progesterone (160 ng/mL) either alone or in combination after pretreatment with estrogen for 24 hours. Decay-accelerating factor expression was analyzed by using reverse transcription–polymerase chain reaction and immunofluorescence microscopy. Expression of progesterone receptors PR-A/B was analyzed by reverse transcription–polymerase chain reaction. RESULTS: Decay-accelerating factor/CD55 levels were found to be significantly increased in ECC1 cells pretreated with estrogen followed by progesterone. Confocal microscopy corroborated protein expression with RNA results. Reverse transcription–polymerase chain reaction analysis of PR-A/B on treatment showed an increase in their expression by twofold when treated with progesterone alone and up to fourfold when treated with a estrogen–progesterone combination. CONCLUSION: These results indicate that progesterone treatment in combination with estrogen increases expression of CD55 endometrial cells, thus altering the dynamics of the inflammatory microenvironment of endometrial cells. A parallel increase in decay-accelerating factor and progesterone expression strongly suggests that progesterone receptor signaling is involved in endometrial decay-accelerating factor expression. These results may explain limitation of progesterone therapy in infertility. This work was supported by Public Health Service grant HD055648 (S.N.), HD041687 (B.N. and S.N.), U54 RR026140 (S.N.), and a CTSA award (UL1TR000445) from the National Center for Advancing Translational Sciences.