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This version published online on July 26, 2007
Endocrinology, doi:10.1210/en.2007-0674
A more recent version of this article appeared on November 1, 2007
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Submitted on May 18, 2007
Accepted on July 16, 2007

Inhibition of premature oocyte maturation: A role for Bone Morphogenetic Protein 15 in zebrafish ovarian follicles

Eric S. Clelland, Qian Tan, Ari Balofsky, Rosie Lacivita, and Chun Peng*

Department of Biology, York University, 4700 Keele St., Toronto, Ontario

* To whom correspondence should be addressed. E-mail: cpeng{at}yorku.ca.

Bone morphogenetic protein-15 (BMP-15) is a member of the TGF-{beta} superfamily known to regulate ovarian functions in mammals. Recently, we cloned zebrafish BMP-15 (zfBMP-15) cDNA and demonstrated that it may play a role in oocyte maturation. In this study, we further investigated the role of BMP-15 in zebrafish follicular development and oocyte maturation using an antiserum developed for zfBMP-15 and by microinjection of follicles with antisense zfBMP-15 N-Morpholino oligonucleotides or an expression construct containing zfBMP-15 cDNA. Injection with antiserum caused a significant decrease in maturation incompetent (insensitive to maturation-inducing hormone (MIH)) early growth phase follicles and a concomitant increase in mature follicles in vivo. In vitro maturation assays showed that incubation with antiserum resulted in a significant increase in oocyte maturation as compared to follicles incubated in preimmune serum or media control. Next, early growth phase follicles were collected and preincubated with either antiserum, preimmune serum or medium control, prior to treatment with MIH or human chorionic gonadotropin (hCG). Antiserum significantly increased oocyte maturation in response to MIH, but not to hCG, and enhanced basal maturation rate in longer term incubations. Knockdown of BMP-15 in early growth stage follicles with an BMP-15 antisense oligonucleotide resulted in increased oocyte maturation, whereas microinjection of BMP-15 cDNA into oocytes significantly reduced MIH- and hCG-induced oocyte maturation in normally competent, mid-growth phase follicles. Collectively, these findings suggest that BMP-15 modulates follicular growth and prevents premature oocyte maturation in zebrafish, in part, by suppressing the sensitivity of follicles to MIH.


Key words: BMP-15 • zebrafish • follicular development • oocyte maturation







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