Ovulation and Luteal Formation in Rodents, Monkeys, and Women

The unifying theme of this P01 proposal is to investigate one of the cornerstones of female fertility, ovulation. We will integrate the individual research projects, both experimentally and technically, to 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 endeavors of 4 separate projects involving 5 investigators that will utilize ovarian tissues from rats, macaques, and women. 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 neovascularization of the nonhuman primate periovulatory follicle. Project #3 (Ko) will study the mechanisms by which progesterone and prostaglandins regulate 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 evident as tissues from women (Project #1) and macaques (Project #2) will be available to extrapolate to rodent models (Projects 1, 3, 4) to the human. 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.