Post-transcriptional gene regulation in the ovary

University Of Kansas Medical Center, Kansas City KS

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The preovulatory surge of LH triggers ovulation, luteinization of granulosa cells and resumption of oocyte meiosis, thereby coordinating multiple cellular and extracellular events with the formation of a "mature" oocyte and corpus luteum. Many downstream events (i.e., cell signaling, transcription) elicited by LH are known, however, little is known about the post-transcriptional regulation of gene expression (mRNA splicing, degradation, localization, initiation of translation) in the periovulatory follicle. The long-term objective of this research is to define the role of post-transcriptional regulation that occurs during rapid differentiation of granulosa cells in the periovulatory follicle to ascertain how transcriptional and post-transcriptional processes mediate ovulation and luteinization. This proposal will "establish an approach" to identify gene transcripts and biochemical pathways undergoing unique post-transcriptional regulation in vivo and will investigate the role specific ribonucleoproteins (RNP) play in ovulation. Aim 1 will profile genes that are associated with the translation machinery of the cell (i.e., an indirect profile of protein synthesis) by expression analysis of polysomal RNA. Aim 2 will demonstrate isolation and identification of gene transcripts that interact with a similar set(s) of RNPs, using antibodies to specific RNPs. Because RNPs coordinate the processes following transcription and provide an address (localization) for mRNAs within the cell, the linkage of unique gene transcripts by association to a specific RNP should allow us to develop informed hypotheses regarding fundamental aspects of post-transcriptional regulation within a novel spatial and temporal context. The proposed research is innovative, in using a translation (polysomal RNA) profiling approach to fill the gaps in the knowledge of genes that direct the process of ovulation and luteinization downstream of the critical endocrine hormone, LH. These in vivo experiments using a mouse model will provide the first description of a hormonal-regulated post-transcriptional mechanism in a mammalian system to date. Contraception and infertility are two major quality of life choices facing women of a reproductive age. Ovulation of a fertilizable oocyte from a mature follicle is fundamental to natural or assisted reproductive strategies and is the critical process disrupted in many infertile women. Inhibition of ovulation is also a primary target for contraceptive technology. These studies will measurably enhance our knowledge of how luteinizing hormone regulates the ovulatory process. The long-term benefits of this research as a basic contribution to understanding ovarian function may ultimately impact the development of more effective contraceptive methods and treatment strategies for infertile women. [unreadable] [unreadable] [unreadable]