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Brain-Derived Neurotrophic Factor: A Novel Human Ovarian Follicular Protein

Department of Obstetrics, Gynecology and Reproductive Sciences (D.B.S., B.F., R.M.S., S.C.), Division of Reproductive Endocrinology and Infertility, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901; and Department of Neuroscience and Cell Biology (C.F.D.), Piscataway, New Jersey 08854-5635

Address all correspondence and requests for reprints to: David B. Seifer, M.D., University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, 303 George Street, Suite 250, New Brunswick, New Jersey 08901.

Abstract

Neurotrophins are a family of soluble polypeptide growth factors widely recognized for their roles in the mammalian nervous system. One such neurotrophin, brain-derived neurotrophic factor (BDNF) was originally described in the nervous system but has now been shown to be expressed in a variety of nonneuronal tissues including endocrine tissues. We examined the human ovarian follicle for its possible secretion of BDNF and further studied mouse oocytes to determine BDNF’s possible influence upon oocyte maturation.

In a series of experiments derived from human specimens from in vitro fertilization following oocyte retrieval, BDNF was detected in human follicular fluid. To define the source of BDNF, cumulus granulosa cells (the cells that immediately surround the developing oocyte) were grown in cell culture for 1–2 d. BDNF protein increased over 24 h in the culture medium. Moreover, the release of BDNF was enhanced upon stimulation with cAMP or forskolin, an activator of cAMP. In contrast, mural granulosa (cells lining the follicle), oocytes, and embryos did not release appreciable quantities of BDNF. To examine possible targets of BDNF, mouse studies were used to localize the BDNF receptor, Trk B, immunocytochemically. The receptor was present on the surface of isolated oocytes. Moreover, BDNF promoted mouse oocyte maturation in culture. These experiments demonstrate for the first time the presence and secretion of BDNF from follicular cells in the human ovary and suggest a possible role for BDNF in the regulation and modulation of oocyte maturation.

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