Keratinocyte growth factor promotes the survival, growth, and differentiation of preantral ovarian follicles

Objective: To determine the effect of treatment with keratinocyte growth fa ctor (KGF) on the survival of cells in cultured preantral follicles and on the growth and differentiation of preantral follicles. Design: Preantral follicles (140-150 mu m) were dissected mechanically from the ovaries of Id,-day-old rats and cultured for 24 hours with and without KGF. Genomic DNA was extracted, labeled with [P-32]-dideoxy adenosine trip hosphate, and fractionated through agarose gels. For growth studies, the fo llicles were cultured individually in 96-well dishes. After 72 hours, the f ollicles were collected and their protein or DNA content was evaluated and their inhibin-a content was determined. Result(s)!: Keratinocyte growth factor suppressed apoptosis in cultured pre antral follicles by 60%. Treatment with KGF or FSH increased follicle diame ter by 8% and 16%, respectively, and combined treatment with KGF and FSH in creased follicle diameter by 16%. Western blot analysis demonstrated increa sed expression of inhibin-a! content after treatment with KGF (2-fold), tre atment with FSH (4-fold), and combined treatment with FSH and KGF (12-fold) , demonstrating the effect of KGF on preantral follicle differentiation. Conclusion(s): Treatment with KGF promotes the survival, growth, and differ entiation of cultured preantral follicles. Keratinocyte growth factor produ ced by theca cells may play a role in the progression of early follicle dev elopment.