Prostaglandins and female reproductive function

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Endocrinology of female reproduction is the general research program conducted in my laboratory. Recognition and establishment of pregnancy in ruminants (cattle) is the most important component and has been funded by NSERC GDP for 26 years. Prostaglandins are key regulators of female reproductive function and particularly involved in the communication between the uterus and the ovary to regulate the duration of the estrous cycle. We have proposed that PGE2 and PGF2a rather than PGF2a alone determines luteolysis or maintenance of the CL at the time of recognition of pregnancy. In the present grant cycle, we will confirm the role of our newly identified PGF synthase AKR1B1, its regulation and feed-back interaction with PGE synthases to effect a tight control of the PGE/PGF ratio. We will study the transit of PGs across cell membranes and tissues through the 2 class of PG transporters SLCO and ABCC proteins using polarized endometrial epithelial cell cultures and its involvement during recognition of pregnancy. While native PGE2 and PGF2a will be assayed by our validated EIA assay, analysis of local vs. systemic inactivation of prostaglandins by PGDH will rely on a newly developed LC/MS system to analyze simultaneously the presence of up to 12 PG metabolites in cell culture medium, blood and uterine tissues. The results obtained with cell cultures will be validated using endometrial explants conditioned in vivo. The validated techniques used in our planned research include qRT-PCR, IHC, Western blotting, culture of polarized epithelial cells on membrane inserts, siRNA, and transient transfection of selected genes.