Volume 13 Issue 5, October 2003: 375-383
ORIGINAL ARTICLES
Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: microtuble organization, asymmetric division and metaphase II arrest
CHAO TONG1, HENG YU FAN1, DA YUAN CHEN1, XIANG FEN SONG1, HEIDE SCHATTEN2, QING YUAN SUN1,*
1State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China. E-mail: sunqy@panda.ioz.ac.cn
2Department of Veterinary Pathobiology, University of Missouri-Columbia, MO 65211, USA.
Correspondence: Qing Yuan SUN(sunqy@panda.ioz.ac.cn)
In this study we used U0126,
a potent and specific inhibitor of MEK, to study the roles of MEK/ERK/p90
rsk signaling pathway in the meiotic cell cycle of mouse oocytes. The phosphorylation
of MAP kinase and p90
rsk in the oocytes treated with 1.5 ?I>M
U0126 was the same as that in oocytes cultured in drug-free medium. With 1.5
?I>M U0126 treatment, the spindles appeared normal as they formed in oocytes,
but failed to maintain its structure. Instead, the spindle lost one pole or
elongated extraordinarily. After further culture, some oocytes extruded gigantic
polar bodies (>30 祄) that later divided into two small ones. Some oocytes
underwent symmetric division and produced two equal-size daughter cells in which
normal spindles formed. In oocytes with different division patterns, MAP kinase
was normally phosphorylated. When the concentration of U0126 was increased to
15 ?I>M, the phosphorylation of both MAPK and p90
rsk were inhibited,
while symmetric division was decreased. When incubating in medium containing
15 ?I>M U0126 for 14 h, oocytes were activated, but part of them failed
to emit polar bodies. MII oocytes were also activated by 15 ?I>M U0126,
at the same time the dephosphorylation of MAP kinase and p90
rsk was
observed. Our results indicate that 1) MEK plays important but not indispensable
roles in microtubule organization; 2) MEK keeps normal meiotic spindle morphology,
targets peripheral spindle positioning and regulates asymmetric division by
activating some unknown substrates other than MAP kinase /p90
rsk;
and 3) activation of MEK/ERK/p90
rsk cascade maintains MII arrest
in mouse oocytes.
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