Adiponectin modulates endometrial prostaglandin production during early pregnancy in pigs: An in vitro study

The peri-implantation period in pigs is critical for establishing pregnancy and is tightly regulated by metabolic and hormonal cues. We hypothesised that adiponectin (ADPN), an adipokine involved in energy homeostasis and insulin sensitivity, modulates the secretion of endometrial prostaglandin (PG) E₂ and F_2α and the expression of apoptotic factors in a pregnancy stage-dependent manner. Additionally, we explored potential interactions between ADPN and insulin (INS) in the regulation of these processes. Endometrial explants from gilts on days 10-11, 12-13, 15-16, and 27-28 of pregnancy, and days 10-12 of the oestrous cycle were cultured with ADPN (1 or 10 µg/mL) and/or INS (10 ng/mL). PG concentrations in culture media and apoptotic markers in tissue homogenates were measured using ELISA. Gene and protein expression of PG synthesis enzymes (COX-2, mPGES-1, AKR1C3, and CBR1) were analysed via qPCR and Western blot, respectively. ADPN modulated PG secretion in a pregnancy stage-dependent manner, stimulating PGE₂ and PGF_2α production during implantation and placentation (days 15-28), likely through the upregulation of COX-2 and/or mPGES-1. In earlier stages, ADPN reduced COX-2 expression but increased the levels of other enzymes without significantly affecting PG output. INS modified the effects of ADPN in a stage-specific manner, suggesting a complex hormonal cross-talk between those hormones. Overall, ADPN exhibited anti-apoptotic properties, although it increased Fas levels at higher concentrations. In conclusion, ADPN regulates PG synthesis and apoptotic signalling in the porcine endometrium in a stage-specific manner, supporting its role in endometrial remodelling, embryo implantation, and early pregnancy maintenance.