Sun Ming-Ju, Zhu Shuai, Li You-Wei, Lin Juan, Gong Shuai, Jiao Guang-Zhong, Chen Fei, Tan Jing-He
College of Life Science, Northeast Agricultural University, Harbin, 150030, P.R. China.
College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai-an City 271018, P.R. China.
Sci Rep. 2016 Mar 24;6:23555. doi: 10.1038/srep23555.
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.
卵母细胞生长/成熟过程中从非包围核仁(NSN)染色质构型向包围核仁(SN)染色质构型转变的机制尚不清楚。本研究通过体外操作酶活性并使用具有高比例NSN构型和延长生发泡期的小卵泡猪卵母细胞来测量重要分子,首次最新确定了卵母细胞内丝裂原活化蛋白激酶(MAPK)在NSN向SN转变中的关键作用。在1 - 2毫米卵泡的卵母细胞内,cAMP水平下降激活MAPK,其通过激活活化B细胞核因子κB轻链增强子(NF-κB)同时抑制组蛋白脱乙酰酶(HDAC)来阻止NSN向SN的转变。在1 - 2毫米卵泡的卵丘细胞中,较低水平的雌二醇和卵母细胞衍生的旁分泌因子(ODPF)降低利钠肽受体2(NPR2),同时增强促卵泡激素(FSH)和cAMP的作用。FSH提高cAMP水平,降低NPR2同时激活MAPK。MAPK关闭缝隙连接,这与NPR2的降低一起,减少环磷酸鸟苷(cGMP)的传递,导致卵母细胞内cAMP水平下降。在3 - 6毫米卵泡中,较高水平的雌二醇和ODPF以及FSH缺乏引发上述事件的逆转,导致卵母细胞内MAPK失活和NSN向SN的转变。