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Neurotrophin-4/5 and Neurotrophin-3 Are Present within the Human Ovarian Follicle but Appear to Have Different Paracrine/Autocrine Functions

Department of Obstetrics, Gynecology, and Reproductive Services (D.B.S., B.F., R.M.S., S.C.), Division of Reproductive Endocrinology and Infertility, University of Medicine and Dentistry of New Jersey (UMDNJ)–Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901; and Department of Neuroscience and Cell Biology (C.F.D.), UMDNJ–Robert Wood Johnson Medical School, 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. E-mail: seiferdb{at}umdnj.edu.

Abstract

Neurotrophins are a family of soluble polypeptide growth factors widely recognized for their role in the mammalian nervous system. We first reported the unique presence of one neurotrophin, brain-derived neurotrophic factor (BDNF), in the follicular fluid of the human ovarian follicle. The BDNF receptor, Trk B, was identified in mouse oocytes, and BDNF accelerated first polar body extrusion in vitro. In the present study, we examined human follicular fluid and mouse immature oocytes to determine whether another Trk B ligand, neurotrophin-4/5 (NT-4/5), is present within the ovarian follicle and if so, whether it demonstrates activity similar to that of BDNF. We also examined whether a non-Trk B neurotrophin ligand, neurotrophin-3 (NT-3), is present within the follicle and has a possible role in oocyte maturation.

NT-4/5 and NT-3 were noted to be present in all human follicular fluid samples aspirated from follicles of women undergoing in vitro fertilization. NT-4/5, but not NT-3, significantly promoted mouse oocyte polar body extrusion. Trk C receptors were not noted to be present in mouse oocytes. This study demonstrates for the first time that NT-4/5 and NT-3 are present in the follicular fluid of the human ovary. These data suggest that NT-4/5, like BDNF, promotes oocyte nuclear maturation. In contrast, NT-3 does not promote oocyte maturation but may contribute to follicle-oocyte maturation by mechanisms not yet identified.

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