Grants and Contracts Details
Successful ovulation is essential for female fertility. However, there remain many gaps in our understanding of exactly how rupture of the ovarian follicle wall and oocyte extrusion occurs, particularly in humans. It is well known that prostaglandins (PGs) play critical roles in the ovulatory process. Studies in various animal models have demonstrated that the LH surge induces the accumulation of PGs in the follicular fluid by increasing the expression of enzymes involved in PG synthesis and transport in periovulatory follicles. However, nothing is known about the mechanisms by which the LH surge increases PGs in human periovulatory follicles. The objectives of the present study are first to characterize the expression pattern of genes involved in PG synthesis and transport in human periovulatory follicles obtained before the LH surge or at defined hours after hCG administration to mimic the natural LH surge in normally cycling women. Secondly, we will determine the regulatory mechanisms by which the LH surge-induced local mediators, progesterone (P4) and EGFs mediate the expression of genes involved in PG synthesis and transport using a human granulosa cell culture model. Our preliminary data revealed that hCG increases the expression of specific PG synthases and transporters and the inhibition of progesterone receptor (PGR) by RU486 and EGF-R by AG1478 reduces the expression of multiple, yet specific genes involved in PG synthesis and transport. Together these data suggest that the hCG-induced upregulated expression of PG synthases and transporters results from coordinate actions of P4/PGR and EGF-signaling in granulosa cells of periovulatory follicles in the human ovary. Not only will this study provide the first comprehensive information of how the LH surge increase PG production in vivo but also cellular and molecular mechanisms by which progesterone/PGR and EGF-signaling coordinate the LH surge-induced accumulation of PGs in periovulatory follicles in the human ovary. The information obtained from the proposed study can be applied to develop more effective and/or efficient methods for birth control as well as strategies to improve the fertility in women.
|Effective start/end date||6/1/16 → 5/31/17|
- Lalor Foundation: $50,000.00
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