Abstract

in the oocyte’s nuclear and cytoplasmic maturation. Though poor oocyte quality is routinely observed in older women, the impact of reproductive aging on GC function has so far not been fully elucidated and, therefore, was subject of this investigation. DESIGN: Prospective case control study. MATERIALS AND METHODS: We examined effects of aging on cell proliferation and gene expression in in vitro cultured human GCs in 4 young oocyte donors (ages 21-30 years), 4 younger (22-37 years) and 4 older (42-47 years) infertility patients. GC proliferation was examined by counting cell number with a hematocytometer, apoptosis by DAPI staining and gene expression by real-time PCR, following in vitro culture in presence or absence of 10IU/ml follicle stimulating hormone (FSH). RESULTS: We observed statistically significantly lower proliferation and higher apoptosis with advancing female age during in vitro culture of GCs. FSH supplementation in culture stimulated GC growth and prevented luteinization, evaluated by FSH receptor and aromatasemRNA expression; but this effect completely dissipated with advancing female age. CONCLUSION: These data demonstrate age-related functional declines in human GCs, characterized by changes in GC luteinization, proliferation, apoptosis and ability to respond to FSH during in vitro culture. Poor oocyte quality in older infertile women may, therefore, at least in part, be related to the loss of normal ovarian GC function. Supported by: Foundation for Reproductive Medicine, Center for Human Reproduction.

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