Prostaglandins and the regulation of female reproductuve function

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Over the last twenty years, NSERC funding allowed to develop several cell culture models derived from the uterus of different animal species to study the mechanisms involved locally during embryo-maternal communication especially with regard to maternal recognition of pregnancy. Across species, the single most remarkable and best conserved property of endometrial cells is their ability to produce specific prostaglandins (PG). PG production within a single cell can be modulated by sex steroids, trophoblastic interferons (IFNtau), oxytocin and platelet activating factor (PAF). In ruminants, PGF2fÑ produced by the endometrial epithelial cells is responsible for the destruction of the corpus luteum and the return to the cycle. On the other hand, PGE2 is antiluteolytic and plays different roles that favor the establishment of pregnancy. At the time of recognition of pregnancy, the embryo must regulate the production of uterine PGs to prevent luteolysis and the return to a new cycle. We have found that in epithelial cells basal PGF2fÑ production was stimulated by oxytocin but switched to PGE2 by IFNtau. Over the last five years, we have identified the functional PGFsynthase of the bovine endometrium as the aldose reductase AKR1B5, an old enzyme with a new function. We have also been the first to propose a role for the newly discovered PG transporter PGT in endocrine action of PGs in the reproductive system. Finally we have shown that the expression of PG receptors in the uterus and corpus luteum closely matches the pattern of expression of biosynthetic and transport proteins. Our findings lead to a new paradigm for the regulation of PG action during maternal recognition of pregnancy. We want to use the next granting period to provide a novel integrated view of PG action in the bovine reproductive system. We will study these systems using cell cultures and tissues collected in vivo under different physiological conditions.  The production of PGs will be analyzed by EIA and the full array of PG metabolites produced from sn-6 and omega-3 fatty acids by GC/MS-MS. Expression of messenger RNA will be done by real time RT-PCR and Northern analysis and protein levels by Western blotting and IHC.