The unifying theme of this P01 proposal is to investigate one of the cornerstones of female fertility, ovulation. Through this P01 project, we will address key questions of the mechanisms associated with follicular rupture and the subsequent early changes in the postovulatory follicle. This will be accomplished through the scientific integration, both experimentally and technically, of 4 separate projects involving 5 investigators that will utilize ovarian tissues from women, macaques, and rodents. Project 1 (Curry/Brannstrom) will make use of an extremely novel model where human follicles are collected across the periovulatory period to examine the changes in the expression of extracellular matrix metalloproteinase inducer (EMMPRIN). Project #2 (Duffy) will take advantage of Dr. Duffy's extensive experience with macaques to investigate the role of PGE2 in angiogenesis of the nonhuman primate periovulatory follicle. Project #3 (Ko) will study the mechanisms by which progesterone regulates leukocyte infiltration in the preovulatory ovary. Project #4 (Jo) will elucidate the cellular action of CIPAR1 in regulating the LH mediated induction of progesterone production. Translational interactions across the projects are readily evident as tissues from women (Project #1) and macaques (Project #2) will be available to extrapolate to rodent models (Projects 1, 3, 4). An Administrative core provides support for the research teams by overseeing the overall functioning of the program as well as coordinating shared tissues from women, macaques and rodents across the different projects. A pilot project will also be supported to open additional avenues of research collaboration and expertise. The significance of this proposal lies in its truly unique translational potential to further our understanding of the pathways that are critical for ovulation and early luteal formation in the human. There can be no stronger translational potential than to use human follicles collected at defined times after hCG to truly comprehend the mechanisms of ovulation and luteinization. The proposed studies in both the human and macaque will make significant strides towards advancing our understanding and treatment of ovulatory associated infertility as well as providing therapeutic modalities to manipulate the ovulatory process in the human thereby providing an important relevance to human health.

Public Health Relevance

The proposed studies will examine the process of oocyte release using unique models and tissues from women, monkeys, and rodents. This will be accomplished by the integration of 4 synergistic and interactive research programs that will together provide a broader, more comprehensive picture of the interrelated mechanisms of ovulation and luteal formation. This information can be used to treat infertility or conversely to explore novel methods of contraception.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
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Application #
Study Section
Special Emphasis Panel (ZHD1-DRG-D (41))
Program Officer
Taymans, Susan
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University of Kentucky
Obstetrics & Gynecology
Schools of Medicine
United States
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Trau, Heidi A; Brännström, Mats; Curry Jr, Thomas E et al. (2016) Prostaglandin E2 and vascular endothelial growth factor A mediate angiogenesis of human ovarian follicular endothelial cells. Hum Reprod 31:436-44
Wilson, Kalin; Park, Jiyeon; Curry Jr, Thomas E et al. (2016) Core Binding Factor-β Knockdown Alters Ovarian Gene Expression and Function in the Mouse. Mol Endocrinol 30:733-47
Cerny, Katheryn L; Ribeiro, Rosanne A C; Jeoung, Myoungkun et al. (2016) Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome. PLoS One 11:e0147685
Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching et al. (2016) Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System. Endocrinology 157:4579-4587
Cacioppo, Joseph A; Koo, Yongbum; Lin, Po-Ching Patrick et al. (2016) Generation of an estrogen receptor beta-iCre knock-in mouse. Genesis 54:38-52
Kim, Soon Ok; Duffy, Diane M (2016) Mapping PTGERs to the Ovulatory Follicle: Regional Responses to the Ovulatory PGE2 Signal. Biol Reprod 95:33
Duffy, Diane M (2015) Novel contraceptive targets to inhibit ovulation: the prostaglandin E2 pathway. Hum Reprod Update 21:652-70
Cerny, K L; Garrett, E; Walton, A J et al. (2015) A transcriptomal analysis of bovine oviductal epithelial cells collected during the follicular phase versus the luteal phase of the estrous cycle. Reprod Biol Endocrinol 13:84
Kim, Soon Ok; Markosyan, Nune; Pepe, Gerald J et al. (2015) Estrogen promotes luteolysis by redistributing prostaglandin F2α receptors within primate luteal cells. Reproduction 149:453-64
Cacioppo, Joseph A; Koo, Yongbum; Lin, Po-Ching Patrick et al. (2015) Generation and characterization of an endothelin-2 iCre mouse. Genesis 53:245-56

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