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State Key Laboratory of Reproductive Biology,3 Institute of Zoology, and Graduate School,4 Chinese Academy of Sciences, Beijing 100101, China
Department of Veterinary Pathobiology,5 University of Missouri-Columbia, Columbia, Missouri 65211
ABSTRACT
The role of androgen and androgen receptors (ARs) in males has been well established. This steroid and its receptor also exist in follicles, but their functions are still unclear. In this study, using a culture system containing a low dose of hypoxanthine, we revealed the positive contribution of testosterone to oocyte meiotic resumption. By performing ultracentrifugation to allow clear visualization of porcine germinal vesicles, our results provide evidence that mitogen-activated protein kinase (MAPK) in the oocyte itself but not in cumulus cells was activated before germinal vesicle breakdown (GVBD) after testosterone treatment. We further explored the signal cascade of testosterone-triggered GVBD and showed significant contributions of AR to testosterone-induced MAPK activation and GVBD. By using a potent and selective inhibitor of SRC and detecting activation of the kinase, we found that testosterone activated SRC in oocytes but not in cumulus cells and that SRC (as an essential upstream molecule of MAPK) mediated this testosterone- and AR-promoted reinitiation of meiosis. The present findings propose an undefined signaling pathway and suggest the potential competence of testosterone for meiotic resumption in mammalian oocytes..
androgen receptor, meiosis, oocyte, signal transduction, testosterone
1Supported in part by grants 2006CB504004 and 2006CB944001 from the National Basic Research Program of China, by grants 30430530 and 30570944 from the National Natural Science Foundation of China, and by project grant KSCX2-YW-R-52 from the Chinese Academy of Sciences Knowledge Innovation.
Correspondence: 2Qing-Yuan Sun, State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, China. FAX: 86 10 64807050; e-mail: sunqy{at}ioz.ac.cn or sunqy1{at}yahoo.com
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