Human chorionic gonadotropin increases serum progesterone, number of corpora lutea and angiogenic factors in pregnant sheep

Early gestation is a critical period when implantation and placental vascularization are established, processes influenced by progesterone (P-4). Although human chorionic gonadotropin (hCG) is not endogenously synthesized by livestock, it binds the LH receptor, stimulating P-4 synthesis. We hypothesized treating pregnant ewes with hCG would increase serum P-4, number of corpora lutea (CLs) and concepti, augment steroidogenic enzymes, and increase membrane P-4 receptors (PAQRs) and angiogenic factors in reproductive tissues. The objective was to determine molecular alterations induced by hCG in pregnant sheep that may promote pregnancy. Ewes received either 600 IU of hCG or saline i.m. on day 4 post mating. Blood samples were collected daily from day 0 until tissue collection for serum P-4 analysis. Reproductive tissues were collected on either day 13 or 25 of gestation and analyzed for PAQRs, CXCR4, proangiogenic factors and steroidogenic enzymes. Ewes receiving hCG had more CL and greater serum P-4, which remained elevated. On day 25, StAR protein production decreased in CL from hCG-treated ewes while HSD3B1 was unchanged; further, expression of CXCR4 significantly increased and KDR tended to increase. PAQR7 and CXCR4 protein was increased in caruncle tissue from hCG-treated ewes. Maternal hCG exposure influenced fetal extraembryonic tissues, as VEGFA, VEGFB, FLT1, and ANGPT1 expression increased. Our results indicate hCG increases serum P-4 due to augmented CL number per ewe. hCG treatment resulted in greater PAQR7 and CXCR4 in maternal endometrium and promoted expression of proangiogenic factors in fetal extraembryonic membranes. Supplementing livestock with hCG may boost P-4 levels and improve reproductive efficiency.