Developmental regulation of prostacyclin synthase and prostacyclin receptors in the ovine uterus and conceptus during the peri-implantation period

Abstract

This study documents the expression of prostacyclin (PGI2) synthase (PTGIS) and PGI2 receptors in the trophoblast and uterus of the ewe at the time of maternal recognition of pregnancy (i.e. days 7, 9, 12, 14 and 17). The membrane receptor for PGI2 (PTGIR) and the nuclear receptors, i.e. peroxisome proliferator-activated receptors (PPAR) and their heterodimer partners the retinoid X receptors (RXR), were analysed. In the endometrium, PTGIS transcript and protein were expressed at day 9 of pregnancy and levels declined from days 12 to 17. Immunohistochemistry andin situhybridization indicated that PTGIS was mainly located in the luminal epithelium of the endometrium. EndometrialPTGIR,PPARA,PPARGandRXRGexpression was regulated during the peri-implantation period whereasPPARD,RXRAandRXRBwere consistently expressed. In the trophoblast,PTGIStranscript levels rose as development progressed and peaked at day 17.PTGIRandPPARAtranscripts peaked before day 12 and then declined and became nearly undetectable by day 17, whereasPPARDandPPARGtranscript levels rose steadily from days 12 to 17. Because thePPARsand theRXRsdisplay different expression profiles, we suggest that different heterodimers may form and support distinct functions as development proceeds. Our results also underline the importance of PTGIS and PPARD in the trophoblast and PTGIR in the uterus, suggesting that PGI2 is of both uterine and trophoblastic origin and is involved in a complex signalling pathway at around the time of implantation in the ewe.