Progesterone receptor membrane component 1 (PGRMC1)-mediated progesterone effect on preimplantation development of in vitro produced porcine embryos

Progesterone is a steroid hormone well known for its significant role in the reproduction process of mammals. Numerous studies have reported on the regulation of progesterone during implantation, pregnancy and parturition, but there are fewer studies on progesterone in relation to the early stages of embryo development. In the present study, we investigated the effects of progesterone during the development of in vitro produced porcine embryos. First, gene expression of various progesterone receptors in the in vitro produced porcine embryos were analyzed. PGRMC1 and PGRMC2 (progesterone receptor membrane component 1 and 2) showed distinct expression. Next, the embryos were treated with two concentrations of progesterone (10 nM and 100 nM) for two different durations (from day 0 and from day 4) to compare the developmental rates, cell numbers, and apoptosis rates of day 7 blastocysts. The experimental groups in both durations showed similarly increased blastocyst cell numbers and decreased apoptosis rates when treated with 100 nM progesterone. Furthermore, the expression levels of PGRMC1, PGRMC2, PAIRBP1 (plasminogen activator inhibitor RNA-binding protein 1), and apoptosis-related genes were examined in blastocysts and showed significant increases in the 100 nM treatment group compared to the control group. Subsequently, the embryos were treated with the PGRMC1 inhibitor, AG-205, and developmental rates, cell numbers, and apoptosis rates of day 7 blastocysts were compared. In addition, 100 nM progesterone was treated simultaneously with AG-205 to test if the inhibition effect is relieved by progesterone. Groups treated with 1 μM and 2 μM AG-205 showed decreased cell numbers and increased apoptosis rates in day 7 blastocysts compared to the control group. We also confirmed the recovery of inhibition by 100 nM progesterone. In conclusion, the present study indicated that progesterone positively affects the development of in vitro produced preimplantation porcine embryos by increasing cell proliferation and decreasing apoptosis via PGRMC1-involved actions. However, the detailed mechanisms of PGRMC1 need further elucidation.