Motola Shmulik, Cao Xiumei, Popliker Malka, Tsafriri Alex
The Bernhard Zondek Hormone Research Laboratory, Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
Mol Reprod Dev. 2008 Oct;75(10):1533-41. doi: 10.1002/mrd.20899.
Gonadotropic stimulation of meiotic resumption in mice is dependent upon mitogen-activated protein kinase (MAPK) activation in the somatic compartment of the follicle. By contrast, spontaneous resumption of meiosis is independent of MAPK activation. In view of the suggested role of meiosis-activating sterol (MAS) in oocyte maturation we have (i) compared MAPK activation in rat preovulatory follicles stimulated by LH or by accumulation of endogenous MAS by using an inhibitor of MAS conversion, AY9944; (ii) examined whether stimulation of meiosis by MAS is dependent upon MAPK activation using denuded oocytes (DO) of Mos- null mice (hereafter Mos(-/-)) with oocytes unable to activate MAPK. Rat preovulatory follicles responded to LH or AY9944 stimulation by MAPK activation. Inhibition of MAPK phosphorylation blocked both LH- and AY9944 triggered resumption of meiosis. In mouse cumulus-enclosed oocytes (CEOs) and DOs AY9944 stimulated GVB in wild-type and Mos(-/-) mouse CEOs cultured with hypoxanthine (Hx). Addition of MAS or AY9944 to mouse DOs cultured with Hx induced resumption of meiosis only in wild-type and Mos(+/-) oocytes, but they were ineffective in Mos(-/-) oocytes. The observed sluggish activation of MAPK induced by AY9944 in rat follicle-enclosed oocytes (FEO) may cause the delay in meiotic resumption in response to MAS and AY9944 stimulation. Further, it is incompatible with the suggested role of MAS as an obligatory mediator of LH in the induction of meiotic maturation. MAPK/MOS activation, whether in the somatic compartment or in denuded oocytes, is required for MAS- like LH-, FSH-, or EGF-induced resumption of meiosis.
小鼠中促性腺激素对减数分裂恢复的刺激取决于卵泡体细胞区有丝分裂原激活蛋白激酶（MAPK）的激活。相比之下，减数分裂的自发恢复不依赖于MAPK激活。鉴于减数分裂激活甾醇（MAS）在卵母细胞成熟中所提出的作用，我们进行了以下研究：（i）通过使用MAS转化抑制剂AY9944，比较了促黄体生成素（LH）刺激的或内源性MAS积累刺激的大鼠排卵前卵泡中的MAPK激活情况；（ii）使用无法激活MAPK的Mos基因敲除小鼠（以下简称Mos(-/-)）的裸卵（DO），研究MAS对减数分裂的刺激是否依赖于MAPK激活。大鼠排卵前卵泡对LH或AY9944刺激的反应是MAPK激活。抑制MAPK磷酸化可阻断LH和AY9944触发的减数分裂恢复。在小鼠卵丘包被卵母细胞（CEO）和DO中，AY9944刺激了与次黄嘌呤（Hx）一起培养的野生型和Mos(-/-)小鼠CEO中的生发泡破裂（GVB）。将MAS或AY9944添加到与Hx一起培养的小鼠DO中，仅在野生型和Mos(+/-)卵母细胞中诱导减数分裂恢复，但在Mos(-/-)卵母细胞中无效。在大鼠卵泡包被卵母细胞（FEO）中观察到的AY9944诱导的MAPK激活迟缓，可能导致对MAS和AY9944刺激的减数分裂恢复延迟。此外，这与MAS作为LH诱导减数分裂成熟的必需介质的作用不符。无论是在体细胞区还是在裸卵中，MAPK/MOS激活都是MAS样LH、FSH或EGF诱导的减数分裂恢复所必需的。
