Although women most commonly give birth to a single baby, many mammalian species are polyovulatory and typically give birth to multiple offspring. Bone morphogenetic protein 15 (BMP-15), which is secreted by oocytes, has been implicated in the regulation of ovulation quota, leading Hashimoto et al. to investigate the role of species-specific differences in the BMP-15 system in determining the ovulation strategies of different species. When expression plasmids encoding the cDNA for either human or mouse BMP-15 were expressed in human 293T cells, human BMP-15 was secreted into the medium, whereas mouse BMP-15 was not. Further analysis revealed defects in mouse BMP-15 proprotein processing in both 293T cells and Chinese hamster ovary (CHO) cells, so that--in contrast to human BMP-15 processing--the mature form of mouse BMP-15 was not produced. Analysis of various mouse-human chimeric proteins indicated that failure to produce mature mouse BMP-15 depended on the proregion of the mouse proprotein, which also reduced but did not prevent production of mature human BMP-15. Thus, the authors suggest that the large litter size characteristic of mice may depend on failure to produce and secrete mature BMP-15.
O. Hashimoto, R. K. Moore, S. Shimaski, Posttranslational processing of mouse and human BMP-15: Potential implication in the determination of ovulation quota. Proc. Natl. Acad. Sci. U.S.A. 102, 5426-5431 (2005). [Abstract] [Full Text]