Submission Number: JOD-4-10-15

Abstract Number: 220

EFFECT OF Bcl-2 ON THE PRIMORDIAL FOLLICLE ENDOWMENT.

Jodi A Flaws* ¹, PA Furth ^2,5, JA Hewitt ^3,6 and AN Hirshfield* ⁴

Dept of Epidemiology & Preventive Medicine, University of Maryland, Baltimore, MD ¹
Depts of Medicine and Physiology, University of Maryland, Baltimore, MD ²
Dept of Microbiology & Immunology, University of Maryland, Baltimore, MD ³
Dept of Anatomy & Neurobiology, University of Maryland, Baltimore, MD ⁴
Institute of Human Virology, University of Maryland, Baltimore, MD ⁵
NIAID, Frederick, MD ⁶

Abstract:
Several members of the Bcl-2 family are expressed in the ovary. The relative expression levels of these proteins are hypothesized to regulate the fate of developing follicles, both prenatally and postnatally. This study tests if simple over-expression of the cell survival protein Bcl-2 in the ovary in FVB/N mice during embryogenesis is sufficient to increase the size of the primordial follicle pool at birth. A 4.8 kb c-kit promoter was used to target Bcl-2 over-expression to the developing follicles. Using this promoter, expression of the bcl-2 transgene should begin during embryogenesis and be maintained through postnatal development. Specifically, at postnatal days (PN) 8 and 30, Bcl-2 expression is 2-fold higher in the low expressing line and 4-fold higher in the high expressing line than in nontransgenic FVB/N mice (controls). On PN 8 and 30, ovaries were collected from the low and high expressing lines and the number of follicles per ovary compared to the levels found in controls. On PN8, over-expression of Bcl-2 appears to increase primordial follicle numbers in a dose dependent manner, but not to affect primary and pre-antral/antral follicle numbers. The low expressing line had 20% more primordial follicles and the high expressing line had 80% more primordial follicles than controls (low expressing = 24,012 890, high expressing = 33,720 1710, controls = 19,502 1439; n = 5-11, p 0.03). By PN30, however, there were no differences in follicle numbers in the transgenics as compared to controls. These results suggest that Bcl-2 over-expression targeted to the ovary during embryogenesis can increase the number of primordial follicles at birth, but that the over-endowment is not maintained beyond puberty. It is interesting to speculate that the ovary may contain a census mechanism by which excess numbers of primordial follicles at birth are detected and removed from the ovary by the onset of puberty. Supported by the Heinz Foundation (JF), NIH CA68033 (PF), and NIH AG13844 (AH). .

Keywords: ovary, bcl-2, follicle

This abstract is being presented at: 1:30 PM in session:
SESSION 9: GENE EXPRESSION DURING FOLLICULAR DEVELOPMENT