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Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells

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, th...

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Autores principales: Ni, Shiwen, Zhang, Teng, Zhou, Chenmin, Long, Min, Hou, Xuan, You, Liji, Li, Hui, Shi, Lanying, Su, You-Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194064/
https://www.ncbi.nlm.nih.gov/pubmed/34124077
http://dx.doi.org/10.3389/fcell.2021.690536
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author Ni, Shiwen
Zhang, Teng
Zhou, Chenmin
Long, Min
Hou, Xuan
You, Liji
Li, Hui
Shi, Lanying
Su, You-Qiang
author_facet Ni, Shiwen
Zhang, Teng
Zhou, Chenmin
Long, Min
Hou, Xuan
You, Liji
Li, Hui
Shi, Lanying
Su, You-Qiang
author_sort Ni, Shiwen
collection PubMed
description 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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spelling pubmed-81940642021-06-12 Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells Ni, Shiwen Zhang, Teng Zhou, Chenmin Long, Min Hou, Xuan You, Liji Li, Hui Shi, Lanying Su, You-Qiang Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-05-28 /pmc/articles/PMC8194064/ /pubmed/34124077 http://dx.doi.org/10.3389/fcell.2021.690536 Text en Copyright © 2021 Ni, Zhang, Zhou, Long, Hou, You, Li, Shi and Su. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Ni, Shiwen
Zhang, Teng
Zhou, Chenmin
Long, Min
Hou, Xuan
You, Liji
Li, Hui
Shi, Lanying
Su, You-Qiang
Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells
title Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells
title_full Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells
title_fullStr Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells
title_full_unstemmed Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells
title_short Coordinated Formation of IMPDH2 Cytoophidium in Mouse Oocytes and Granulosa Cells
title_sort coordinated formation of impdh2 cytoophidium in mouse oocytes and granulosa cells
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194064/
https://www.ncbi.nlm.nih.gov/pubmed/34124077
http://dx.doi.org/10.3389/fcell.2021.690536
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