期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 15, 页码 5426-5431出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0409533102
关键词
ovary; oocyte; folliculogenesis; TGF-beta superfamily; pregnancy
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.
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