The mammalian oocyte, like that of all other organisms, occupies a unique position in the life history of the species, for it is absolutely essential for the continuity of life from one generation to the next. Folliculogenesis is a precise series of developmental events that requires the cooperative efforts of several cell types comprising the Graafian follicle ant the integration and modulation of a complex set of chemical messages that ultimately insure maturation and survival of the oocyte and finally bring about its ovulation. Basic to any attempt to elucidate the integrated functions of the developing Graafian follicle resides in the understanding of the unique structural and physiological features of each component. A defect in one cell type or one component may have marked repercussions on another constituent. The objective of this proposal is to learn some of the basic, fundamental aspects of the dynamic morphology and function of the oocyte and multifunctional granulosa cell as it is related to follicular development under normal and experimental conditions.
The specific aims of the proposal are: (A) to determine how to granulosa cell subclasses regulate the fate of the follicle in a reconstituted model system. (B) To determine the effects of stromal tissue on differentiative properties of large and small granulosa cells. (C) To characterize the transformation of granulosa cells during cystogenesis and to evaluate the role of the basement membrane in the process. (D) To characterize macromolecules of the follicular microenvironment in relation to ongoing oogenesis, folliculogenesis or cystogenesis. The proposed experiments will use in vivo and in vitro techniques, bicameral culture system, light and electron microscopy, immunocytochemical methods, radioimmunoassay, colloidal gold-protein A immunocytochemical methods, biochemical techniques, and computer technology. The expected fundamental data will be integrated with that obtained about the reproductive process in general through other biological disciplines.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD014574-13
Application #
3312686
Study Section
Reproductive Biology Study Section (REB)
Project Start
1980-07-01
Project End
1993-05-31
Budget Start
1992-06-01
Budget End
1993-05-31
Support Year
13
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Fissore, R A; Longo, F J; Anderson, E et al. (1999) Differential distribution of inositol trisphosphate receptor isoforms in mouse oocytes. Biol Reprod 60:49-57
Lee, G Y; Croop, J M; Anderson, E (1998) Multidrug resistance gene expression correlates with progesterone production in dehydroepiandrosterone-induced polycystic and equine chorionic gonadotropin-stimulated ovaries of prepubertal rats. Biol Reprod 58:330-7
Anderson, E; Lee, G Y; O'Brien, K (1997) Polycystic ovarian condition in the dehydroepiandrosterone-treated rat model: hyperandrogenism and the resumption of meiosis are major initial events associated with cystogenesis of antral follicles. Anat Rec 249:44-53
Thompson, W E; Sanbuissho, A; Lee, G Y et al. (1997) Steroidogenic acute regulatory (StAR) protein (p25) and prohibitin (p28) from cultured rat ovarian granulosa cells. J Reprod Fertil 109:337-48
Anderson, E; Lee, G Y (1997) The polycystic ovarian (PCO) condition: apoptosis and epithelialization of the ovarian antral follicles are aspects of cystogenesis in the dehydroepiandrosterone (DHEA)-treated rat model. Tissue Cell 29:171-89
Yan, Z; Lee, G Y; Anderson, E (1997) Influence of dehydroepiandrosterone on the expression of insulin-like growth factor-1 during cystogenesis in polycystic rat ovaries and in cultured rat granulosa cells. Biol Reprod 57:1509-16
Anderson, E; Lee, G Y (1996) The effects of dehydroepiandrosterone (DHEA) and its metabolites on the polycystic ovarian condition (PCO): cystogenic changes of rat granulosa cells in vitro. Tissue Cell 28:673-85
Rao, I M; Gadson Jr, P F; Anderson, E et al. (1993) Characterization of progesterone biosynthesis in a transformed granulosa cell line. Mol Cell Endocrinol 94:121-8
Yeh, J; Lee, G Y; Anderson, E (1993) Presence of transforming growth factor-alpha messenger ribonucleic acid (mRNA) and absence of epidermal growth factor mRNA in rat ovarian granulosa cells, and the effects of these factors on steroidogenesis in vitro. Biol Reprod 48:1071-81
Anderson, E; Lee, G Y (1993) The participation of growth factors in simulating the quiescent, proliferative, and differentiative stages of rat granulosa cells grown in a serum-free medium. Tissue Cell 25:49-72

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