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An essential role for the intra-oocyte MAPK activity in the NSN-to-SN transition of germinal vesicle chromatin configuration in porcine oocytes

机译:卵母细胞内MAPK活性在猪卵母细胞生小泡染色质构型从NSN到SN过渡中的重要作用

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摘要

The mechanisms for the transition from non-surrounded nucleolus (NSN) to surrounded nucleolus (SN) chromatin configuration during oocyte growth/maturation are unclear. By manipulating enzyme activities and measuring important molecules using small-follicle pig oocytes with a high proportion of NSN configuration and an extended germinal vesicle stage in vitro, this study has the first time up-to-date established the essential role for intra-oocyte mitogen-activated protein kinase (MAPK) in the NSN-to-SN transition. Within the oocyte in 1–2 mm follicles, a cAMP decline activates MAPK, which prevents the NSN-to-SN transition by activating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) while inhibiting histone deacetylase (HDAC). In cumulus cells of 1–2 mm follicles, a lower level of estradiol and oocyte-derived paracrine factor (ODPF) reduces natriuretic peptide receptor 2 (NPR2) while enhancing FSH and cAMP actions. FSH elevates cAMP levels, which decreases NPR2 while activating MAPK. MAPK closes the gap junctions, which, together with the NPR2 decrease, reduces cyclic guanosine monophosphate (cGMP) delivery leading to the cAMP decline within oocytes. In 3–6 mm follicles, a higher level of estradiol and ODPF and a FSH shortage initiate a reversion of the above events leading to MAPK inactivation and NSN-to-SN transition within oocytes.
机译:卵母细胞生长/成熟过程中从非环绕核仁(NSN)过渡到周围核仁(SN)染色质构型的机制尚不清楚。通过操纵酶活性并使用具有较高NSN构型比例的小卵泡猪卵母细胞并在体外延长生胚泡阶段来测量重要分子,这项研究首次首次确定了卵母细胞内促细胞分裂剂的重要作用激活的蛋白激酶(MAPK)从NSN过渡到SN。在1-2mm卵泡的卵母细胞中,cAMP下降激活MAPK,从而通过激活被激活的B细胞核因子κ轻链增强子(NF-κB)阻止了NSN向SN的转变,同时抑制组蛋白去乙酰化酶( HDAC)。在1-2mm卵泡的卵丘细胞中,较低水平的雌二醇和卵母细胞旁分泌因子(ODPF)会减少利钠肽受体2(NPR2),同时增强FSH和cAMP的作用。 FSH升高cAMP水平,从而在激活MAPK时降低NPR2。 MAPK关闭间隙连接,这与NPR2的减少一起减少了环鸟苷单磷酸(cGMP)的传递,导致卵母细胞内cAMP的下降。在3–6mm的卵泡中,较高水平的雌二醇和ODPF以及FSH缺乏引发上述事件的逆转,从而导致卵母细胞内MAPK失活和NSN向SN过渡。

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