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PNAS 102 (15): 5426-5431

Copyright © 2005 by the National Academy of Sciences.


Posttranslational processing of mouse and human BMP-15: Potential implication in the determination of ovulation quota

Osamu Hashimoto, R. Kelly Moore, and Shunichi Shimasaki *

Department of Reproductive Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093-0633

Edited by Ian Wilmut, Roslin Institute, Midlothian, United Kingdom, and approved March 8, 2005

Received for publication December 22, 2004.

Abstract: There has been significant attention to the growing recognition that oocytes have a critical capacity to organize and govern surrounding somatic cells. Bone morphogenetic protein 15 (BMP-15) is an oocyte-secreted factor that has raised particular interest due to its established role in determining ovulation quota and female fertility in mammals. As a first step in determining whether there are species-specific differences in the BMP-15 system that may play causal roles in the differences in ovulation quota observed in different mammalian species, we here compare the molecular characteristics of BMP-15 of polyovulatory mice with that of monoovulatory humans. We found that, although human BMP-15 mature protein is readily produced, there are defects in the production of mouse BMP-15 mature protein in an in vitro system of transfected cells. The generation of chimeric constructs consisting of different combinations of mouse and human BMP-15 proregions, cleavage sites, and mature regions indicates that the defects in the production of mouse BMP-15 mature protein depend on the presence of the mouse BMP-15 proregion. The mouse proregion also caused a significant reduction in the production of human BMP-15 mature protein. The coexpression with a convertase cleavage enzyme, furin, results in complete processing of all these chimeras; however, no mouse mature protein is detected in either secreted or cell-confined forms except when associated with the human proregion. Based on the biological role of BMP-15, defects in the production of mouse BMP-15 mature protein could correlate with the high ovulation quota and litter size observed in mice.

Key Words: ovary • oocyte • folliculogenesis • TGF-{beta} superfamily • pregnancy

Author contributions: S.S. designed research; O.H. and R.K.M. performed research; and R.K.M. and S.S. wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: BMP-15, bone morphogenetic protein 15; GDF-9, growth and differentiation factor 9.

* To whom correspondence should be addressed. E-mail: sshimasaki{at}

© 2005 by The National Academy of Sciences of the USA

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