论文成果
Coordinated formation of IMPDH2 cytoophidium in mouse oocytes and granulosa cells.
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发表刊物：
Frontiers in Cell and Developmental Biology
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刊物所在地：
CH
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关键字：
IMPDH2,cytoophidium,female fertility,granulosa cell,guanine nucleotide,mycophenolic acid,oocyte maturation
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摘要：
Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme catalyzing de novo biosynthesis of guanine nucleotides, aggregates under certain circumstances into a type of non-membranous filamentous macrostructure termed "cytoophidium" or "rod and ring" in several types of cells. However, the biological significance and underlying mechanism of IMPDH assembling into cytoophidium remain elusive. In mouse ovaries, IMPDH is reported to be crucial for the maintenance of oocyte-follicle developmental synchrony by providing GTP substrate for granulosa cell natriuretic peptide C/natriuretic peptide receptor 2 (NPPC/NPR2) system to produce cGMP for sustaining oocyte meiotic arrest. Oocytes and the associated somatic cells in the ovary hence render an exciting model system for exploring the functional significance of formation of IMPDH cytoophidium within the cell. We report here that IMPDH2 cytoophidium forms in vivo in the growing oocytes naturally and in vitro in the cumulus-enclosed oocytes treated with IMPDH inhibitor mycophenolic acid (MPA). Inhibition of IMPDH activity in oocytes and preimplantation embryos compromises oocyte meiotic and developmental competences and the development of embryos beyond the 4-cell stage, respectively. IMPDH cytoopidium also forms in vivo in the granulosa cells of the preovulatory follicles after the surge of luteinizing hormone (LH), which coincides with the resumption of oocyte meiosis and the reduction of IMPDH2 protein expression. In cultured COCs, MPA-treatment causes the simultaneous formation of IMPDH cytoopidium in cumulus cells and the resumption of meiosis in oocytes, which is mediated by the MTOR pathway and is prevented by guanosine supplementation. Therefore, our results indicate that cytoophidia do form in the oocytes and granulosa cells at particular stages of development, which may contribute to the oocyte acquisition of meiotic and developmental competences and the induction of meiosis re-initiation by the LH surge, respectively.
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全部作者：
Teng Zhang,Chenmin Zhou,Min Long,Xuan Hou,Hui Li,Lanying Shi,
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第一作者：
Shiwen Ni
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论文类型：
Research Article
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通讯作者：
YouQiang Su
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论文编号：
10.3389/fcell.2021.690536
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卷号：
9
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期号：
690536
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页面范围：
45672
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ISSN号：
2296-634X
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是否译文：
否
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发表时间：
2021-05-28
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