Su You-Qiang, Wigglesworth Karen, Pendola Frank L, O'Brien Marilyn J, Eppig John J
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Endocrinology. 2002 Jun;143(6):2221-32. doi: 10.1210/endo.143.6.8845.
This study investigated the participation of MAPK in the resumption of meiosis [germinal vesicle breakdown (GVB)] in oocytes and cumulus expansion using oocyte-cumulus cell complexes (OCC) from Mos-null mice (Mos(tm1Ev)/Mos(tm1Ev), hereafter Mos(-/-)). MAPK activity was not detected in Mos(-/-) oocytes whether they matured in vivo or in vitro, with or without gonadotropin stimulation. Therefore, there are no pathways independent of MOS that activate MAPK during gonadotropin-induced maturation. In contrast, MAPK activity was always detected coincident with GVB in Mos(+/+) oocytes. Moreover, MAPK activity was detected in cumulus cells before gonadotropin-induced GVB in OCC regardless of genotype. A specific inhibitor (U0126) of MEK, a MAPKK required for MAPK activity, inhibited gonadotropin-induced GVB in OCC of both Mos(+/+) and Mos(-/-) mice. Activation of MAPK was downstream of elevation of cAMP. U0126 also inhibited cumulus expansion stimulated by FSH, epidermal growth factor, 8-bromo-cAMP, and recombinant growth differentiation factor-9. It is concluded that under the in vitro conditions used here, gonadotropin-induced GVB requires the participation of MAPK activity in the cumulus cells, but not in the oocyte. Moreover, the induction of cumulus expansion also requires the participation of MAPK, and this action is downstream of both elevation of cAMP and growth differentiation factor-9.
本研究利用Mos基因敲除小鼠（Mos(tm1Ev)/Mos(tm1Ev)，以下简称Mos(-/-)）的卵母细胞-卵丘细胞复合体（OCC），研究了丝裂原活化蛋白激酶（MAPK）在卵母细胞减数分裂恢复[生发泡破裂（GVB）]和卵丘扩展中的作用。无论是否有促性腺激素刺激，Mos(-/-)卵母细胞在体内或体外成熟时均未检测到MAPK活性。因此，在促性腺激素诱导的成熟过程中，不存在独立于MOS激活MAPK的途径。相比之下，在Mos(+/+)卵母细胞中，MAPK活性总是与GVB同时被检测到。此外，无论基因型如何，在促性腺激素诱导OCC发生GVB之前，卵丘细胞中均可检测到MAPK活性。MEK是MAPK活性所需的一种丝裂原活化蛋白激酶激酶（MAPKK），其特异性抑制剂（U0126）可抑制Mos(+/+)和Mos(-/-)小鼠OCC中促性腺激素诱导的GVB。MAPK的激活位于cAMP升高的下游。U0126还可抑制促卵泡素（FSH）、表皮生长因子、8-溴-cAMP和重组生长分化因子-9刺激的卵丘扩展。研究得出结论，在此处使用的体外条件下，促性腺激素诱导的GVB需要卵丘细胞而非卵母细胞中的MAPK活性参与。此外，卵丘扩展的诱导也需要MAPK的参与，且此作用位于cAMP升高和生长分化因子-9的下游。
