Our long-term goal is to further our understanding of the molecular mechanisms by which FSH initiates ovarian follicular development. Following the elevation of intracellular cAMP levels by FSH, the adenylyl cyclase enzyme exhibits a transient attenuation response.
In specific aim one, we will investigate possible mechanisms responsible for the transient attenuation of the granulosa cell adenylate cyclase enzyme. cAMP Induces all of the differentiation-associated effects in immature granulosa cells attributed to FSH; thus cAMP Is believed to mediate these actions of FSH. Yet, identification and characterization of the enzymes which mediate the effects of cAMP, the cAMP dependent protein kinases, is not available. In the next three specific aims, we will identify the subunit composition of the cAMP-dependent protein kinases present in immature porcine granulosa cells, we will elucidate the acute regulation of this enzyme by cAMP in response to FSH, and we will identify proteins which are phosphorylated in this cascade. Although relatively low levels of cAMP are needed to promote granulosa cell maturation, pharmacologically high levels of cAMP are not deleterious.
In specific aim five we will investigate mechanisms which protect the granulosa cells from excessively high intracellular cAMP levels. It is hoped that these studies will extend our understanding of the molecular mechanisms by which FSH via cAMP regulates granulosa cell function.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1996
Total Cost
Indirect Cost
Que, Emily L; Duncan, Francesca E; Bayer, Amanda R et al. (2017) Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy. Integr Biol (Camb) 9:135-144
Vanorny, Dallas A; Mayo, Kelly E (2017) The role of Notch signaling in the mammalian ovary. Reproduction 153:R187-R204
Xiao, Shuo; Duncan, Francesca E; Bai, Lu et al. (2015) Size-specific follicle selection improves mouse oocyte reproductive outcomes. Reproduction 150:183-92
Que, Emily L; Bleher, Reiner; Duncan, Francesca E et al. (2015) Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks. Nat Chem 7:130-9
Xiao, Shuo; Zhang, Jiyang; Romero, Megan M et al. (2015) In vitro follicle growth supports human oocyte meiotic maturation. Sci Rep 5:17323
Cordeiro, Marília H; Kim, So-Youn; Ebbert, Katherine et al. (2015) Geography of follicle formation in the embryonic mouse ovary impacts activation pattern during the first wave of folliculogenesis. Biol Reprod 93:88
Kong, Betty Y; Duncan, Francesca E; Que, Emily L et al. (2015) The inorganic anatomy of the mammalian preimplantation embryo and the requirement of zinc during the first mitotic divisions. Dev Dyn 244:935-47
Kim, So-Youn; Ebbert, Katherine; Cordeiro, Marilia H et al. (2015) Cell autonomous phosphoinositide 3-kinase activation in oocytes disrupts normal ovarian function through promoting survival and overgrowth of ovarian follicles. Endocrinology 156:1464-76
Hong, Young Pyo; Gleber, Sophie-Charlotte; O'Halloran, Thomas V et al. (2014) Alignment of low-dose X-ray fluorescence tomography images using differential phase contrast. J Synchrotron Radiat 21:229-34
Kong, B Y; Duncan, F E; Que, E L et al. (2014) Maternally-derived zinc transporters ZIP6 and ZIP10 drive the mammalian oocyte-to-egg transition. Mol Hum Reprod 20:1077-89

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