Developmental programming: impact of prenatal testosterone excess on ovarian cell proliferation and survival factors

PADMANABHAN, V; SALVETTI NR; VEIGA-LOPEZ A; ORTEGA HH

Portland

Congreso; 44th Annual Meeting, Society for the Study of Reproduction (SSR); 2011

Society for the Study of Reproduction (SSR)

Prenatal testosterone (T) excess leads to reproductive dysfunctions in sheep culminating in progressive loss of cyclicity. At the follicular level, prenatal T excess induces 1) selective increase in androgen receptor in the stroma and granulosa cells of fetal days 90 and 140 ovaries as well as antral follicles of 10- and 21-month-old females, 2) an increase in estrogen receptor (ESR) 1 and decrease in ESR2 in granulosa cells of antral follicles of 10- and 21-month-old females, and 3) an increase in ovarian follicular recruitment and persistence resulting in multifollicular ovarian morphology. The factors contributing to follicular persistence in prenatal T-treated sheep are unknown. We hypothesized that prenatal T excess disrupts the developmental ontogeny of ovarian proliferation and apoptotic factors, thus contributing to the development of follicular persistence. Pregnant Suffolk sheep were given T propionate, 100 mg i.m. twice weekly, in cottonseed oil from days 30-90 of gestation. Changes in developmental expression of proliferating cell nuclear antigen (PCNA), antiapoptotic protein B-cell lymphoma 2 (Bcl-2), and proapoptotic protein Bcl-2–associated X protein (BAX) were determined in ovarian sections using streptavidin-biotin immunoperoxidase method at the following time points: fetal (days 90 and 140), prepubertal (22 weeks), end of first breeding (10 months), and second breeding (21 months) season (n=4-7/per age/treatment group). Image analysis was performed using Image Pro-Plus 3.0.1 system. Analyses of data (ANOVA, followed by Duncan’s multiple range tests) found age, follicle, and tissue specific changes in expression of PCNA, BAX, and Bcl-2 protein. Prenatal T treatment induced a) an increase (p