Prostacyclin receptor (PTGIR) in the porcine endometrium: Regulation of expression and role in luminal epithelial and stromal cells

The prostacyclin (PGI2) signaling pathway plays an important role during early pregnancy in rodents and ruminants. Abundant concentrations of PGI2 were also found in the endometrium and uterine lumen of gilts during the period of implantation. The present study was designed to examine (1) the expression of PGI2 receptor (PTGIR) messenger RNA (mRNA) and protein in the endometrium of cyclic and early-pregnant gilts; (2) possible regulation of endometrial PTGIR gene expression by conceptus products, estradiol and cytokines; (3) the effect of iloprost (a PGI2 analogue) on cAMP formation and the expression of fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF; isoform 164) mRNA in luminal epithelial (LE) and stromal (ST) cells. Increased PTGIR mRNA expression in the endometrium was detected on Days 11 to 12 and 18 to 20 of pregnancy compared with respective days of the estrous cycle (P < 0.05). Moreover, greater PTGIR protein level was observed in pregnant than in cyclic gilts on Days 11 to 12 after estrus (P < 0.05). Gilts with unilateral pregnancy revealed abundant PTGIR expression in the endometrium collected from the gravid uterine horn of Day-11 pregnant gilts compared with the respective horn of cyclic animals (P < 0.01). Both LE and ST cells of the endometrium possess PTGIR protein. Moreover, IL1β, IFNγ, and conceptus-exposed medium, but not estradiol, stimulated PTGIR mRNA expression in LE and ST cells in vitro. Activation of PTGIR by incubation of LE and ST cells with iloprost resulted in greater cAMP generation (P < 0.01). Moreover, iloprost increased FGF-2 and VEGF164 mRNA expression in ST (P < 0.05), but not LE cells. In conclusion, this study revealed increased expression of PTGIR in the porcine endometrium during the peri-implantation period and reported a possible regulation of PTGIR abundance by conceptus-derived factors. Moreover, besides its important role in vascular system, PGI2 may promote the expression of proangiogenic genes in the uterine stroma.