Testosterone potentially triggers meiotic resumption by activation of intra-oocyte SRC and MAPK in porcine oocytes.
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.
Li
Mo
M
State Key Laboratory of Reproductive Biology, Institute of Zoology, and Graduate School, Chinese Academy of Sciences, Beijing 100101, China.
Ai
Jun-Shu
JS
Xu
Bao-Zeng
BZ
Xiong
Bo
B
Yin
Shen
S
Lin
Sheng-Li
SL
Hou
Yi
Y
Chen
Da-Yuan
DY
Schatten
Heide
H
Sun
Qing-Yuan
QY
D000818:Animals; D002070:Butadienes; D054885:Cumulus Cells / Q000378:metabolism; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D019271:Hypoxanthine / Q000378:metabolism; D008540:Meiosis; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009570:Nitriles; D009865:Oocytes / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011743:Pyrimidines; D011944:Receptors, Androgen / Q000378:metabolism*; D013552:Swine; D013739:Testosterone / Q000502:physiology*; D018909:src Homology Domains
C412373:AG 1879; D002070:Butadienes; D009570:Nitriles; D011743:Pyrimidines; D011944:Receptors, Androgen; C113580:U 0126; D019271:Hypoxanthine; D013739:Testosterone; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases