Prostaglandins as Mediators of the Conceptus-Maternal Interactions During Peri-implantation Period.

Abstract

Ovarian progesterone induces changes leading to a temporary state of uterine receptivity for conceptus implantation. Estrogen produced by the porcine conceptus on days 11-12 of pregnancy, provide the primary signal for the maternal recognition of pregnancy and prolongs luteal progesterone production. In pigs, as in other species, implantation and establishment of pregnancy is associated with up-regulation of expression of proinflammatory factors, including cytokines, growth factors and prostaglandins (PGs), that probably activate inflammatory pathways in endometrium. Moreover, PGF2alpha and PGE2 exert an opposite action on corpus luteum. Therefore, a control over their synthesis and secretion is involved either in the initiation of luteolysis, or pregnancy establishment. One of the supportive mechanisms by which the porcine conceptus inhibits luteolysis is changing PG synthesis in favour of luteoprotective PGE2. We have found that selective changes in PG synthesis enzymes are regulated by estrogen. Using gene silencing PGE2 synthase (mPGES-1) in endometrial cells, we indicated an interdependence between the expression of this enzyme and PGE2 receptor, PTGER2. Moreover, we have established that PGE2 through endometrial PTGER2 elevates expression of enzymes involved in PGE2 synthesis, as well as endometrial and trophoblast PTGER2. These findings lead to the suggestion that conceptus PGE2 could be amplified by PGE2 feedback loop in endometrium. After reaching ovaries, PGE2 may act through luteal PTGER2 and PTGER4. On the other hand, elevated endometrial and trophoblast synthesis of PGE2 could have a direct effect to promote uterine function and conceptus development. We found that expression of PTGER2 is up-regulated in the endometrium on days 11-12 of pregnancy and in the trophoblast during implantation period. Now, we have used in vivo model to elucidate local and systemic effects of conceptus on endometrial gene expression. Understanding mechanisms of pregnancy establishment requires establishment of a hierarchy and timing of molecular relationships in the maternal-conceptus cross-talk. Supported by the State Committee for Scientific Research in Poland grants (DWM/N106/COST/2008 and NN311319135) and the basic grant of the Institute (IRZBZ PAN-2008-ZMDH). (platform)