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Activin from Secondary Follicles Causes Small Preantral Follicles to Remain Dormant at the Resting Stage

Department of Obstetrics and Gynecology (H.M., X.L., K.A., J.K., K.Y., H.Y., Y.I.), Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan; and Laboratory Animal Science (Y.H.), Kitasato University School of Veterinary Medicine and Animal Science, Towada, Aomori 034-8628, Japan

Address all correspondence and requests for reprints to: Hideki Mizunuma, Department of Obstetrics and Gynecology, Gunma University School of Medicine, 3–39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan. E-mail: mizunuma{at}news.sb.gunma-u.ac.jp

The purpose of the present study was to investigate 1) whether activin A can cause primary follicles to become dormant at the resting stage, and 2) the role of the secondary follicle on follicular growth of primary follicles. Preantral follicles (100–120 µm in diameter) harvested from adult mice and cultured in in vitro follicle culture system showed a significant increase in size and estrogen and inhibin secretion in response to FSH, but the administration of activin A blocked the effect of FSH. Withdrawal of activin A not only restored the follicular response to FSH but also enhanced the effect of FSH, indicating that the action of activin A is to cause small preantral follicles to become dormant at the preantral stage. To investigate the role of secondary follicles in early folliculogenesis, small preantral follicles were cocultured with secondary follicle (300–350 µm in diameter) in the presence of FSH. The secondary follicle showed a significant increase in follicular diameter as a result of stimulation by FSH, but the small preantral follicles did not increase in size. After removal of the secondary follicle, however, the small preantral follicles commenced follicular growth, indicating that the growth of small preantral follicles is suppressed by the secondary follicle. Administration of the activin binding protein follistatin caused a significant increase in follicular diameter of both small preantral and secondary follicles as a result of stimulation by FSH. These results have suggested that secondary follicles cause primary follicles to become dormant at the resting stage by secreting activin.

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