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Transforming growth factor-β: its role in ovarian follicle development

D Rosairo, Prince Henry's Institute of Medical Research, Clayton, Australia
I Kuyznierewicz, Prince Henry's Institute of Medical Research, Clayton, Australia
J Findlay, Prince Henry's Institute of Medical Research, Clayton, Australia
A Drummond, Prince Henry's Institute of Medical Research, Clayton, Australia

Correspondence: Ann Drummond, Email: ann.drummond{at}princehenrys.org

Abstract

Ovarian follicular growth and differentiation in response to transforming growth factor-β (TGF-β) was investigated using using postnatal and immature ovarian models. TGF-β ligand and receptor mRNAs were present in the rat ovary 4-12 days after birth and at day 25. In order to assess the impact of TGF-β1 on follicle growth and transition from the primordial through to the primary and preantral stages of development we established organ cultures with 4 day old rat ovaries. After 10 days in culture with follicle stimulating hormone (FSH), TGF-β1, or a combination of the two, ovarian follicle numbers were counted and an assessment of atresia was undertaken using TUNEL. Preantral follicle numbers declined significantly when treated with the combination of FSH and TGF-β1, consistent with our morphological appraisal suggesting an increase in atretic primary and preantral follicles. To investigate the mechanisms behind the actions of TGF-β1 we isolated granulosa cells and treated them with FSH and TGF-β1. Markers of proliferative, steroidogenic and apoptotic capacity were measured by real-time PCR. Cyclin D2 mRNA expression by granulosa cells was significantly increased in response to the combination of FSH and TGF-β1. The expression of forkhead homolog in rhabdomyosarcoma (FKHR) mRNA by granulosa cells was significantly reduced in the presence of both FSH and TGF-β1, individually and in combination regimes. In contrast, the expression of steroidogenic enzymes/proteins was largely unaffected by TGF-β1. These data suggest an inhibitory role for TGF-β1 (in the presence of FSH) in follicle development and progression.