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JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice
In female mammals, primordial follicles consist of two types of cells, namely, oocytes and pregranulosa cells that surround the oocytes. The size of the primordial follicle pool determines the reproductive ability of female mammals. However, the underlying mechanisms controlling primordial follicle...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827266/ https://www.ncbi.nlm.nih.gov/pubmed/29242197 http://dx.doi.org/10.1242/bio.029470 |
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author | Huang, Kun Wang, Ye Zhang, Tuo He, Meina Sun, Guanghong Wen, Jia Yan, Hao Cai, Han Yong, Changfu Xia, Guoliang Wang, Chao |
author_facet | Huang, Kun Wang, Ye Zhang, Tuo He, Meina Sun, Guanghong Wen, Jia Yan, Hao Cai, Han Yong, Changfu Xia, Guoliang Wang, Chao |
author_sort | Huang, Kun |
collection | PubMed |
description | In female mammals, primordial follicles consist of two types of cells, namely, oocytes and pregranulosa cells that surround the oocytes. The size of the primordial follicle pool determines the reproductive ability of female mammals. However, the underlying mechanisms controlling primordial follicle assembly remain unclear. In this study, we show that oocyte-derived Janus kinase (JAK) signaling is vital for germline cyst breakdown and primordial follicle formation in vitro. JAK2 and JAK3 activity is increased while germline cysts are breaking down. Inhibition of either JAK2 or JAK3 prevents germline cyst breakdown and primordial follicle formation. We further show that specific suppression of JAK2 delays germ cell loss through the downregulation of p53, but has no influence on pregranulosa cell proliferation. Alternatively, specific inhibition of JAK3 decreases pregranulosa cell proliferation by downregulating Notch2 signaling, implying that JAK3 acts on pregranulosa cells by controlling the extracellular secretion of oocyte-derived factors. In summary, our results indicate that JAK signaling contributes to germline cyst breakdown and primordial follicle formation by regulating oocyte loss and pregranulosa cell proliferation in the fetal mouse ovary. Our findings contribute to a better understanding of the molecular mechanism of mammalian folliculogenesis. |
format | Online Article Text |
id | pubmed-5827266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-58272662018-02-28 JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice Huang, Kun Wang, Ye Zhang, Tuo He, Meina Sun, Guanghong Wen, Jia Yan, Hao Cai, Han Yong, Changfu Xia, Guoliang Wang, Chao Biol Open Research Article In female mammals, primordial follicles consist of two types of cells, namely, oocytes and pregranulosa cells that surround the oocytes. The size of the primordial follicle pool determines the reproductive ability of female mammals. However, the underlying mechanisms controlling primordial follicle assembly remain unclear. In this study, we show that oocyte-derived Janus kinase (JAK) signaling is vital for germline cyst breakdown and primordial follicle formation in vitro. JAK2 and JAK3 activity is increased while germline cysts are breaking down. Inhibition of either JAK2 or JAK3 prevents germline cyst breakdown and primordial follicle formation. We further show that specific suppression of JAK2 delays germ cell loss through the downregulation of p53, but has no influence on pregranulosa cell proliferation. Alternatively, specific inhibition of JAK3 decreases pregranulosa cell proliferation by downregulating Notch2 signaling, implying that JAK3 acts on pregranulosa cells by controlling the extracellular secretion of oocyte-derived factors. In summary, our results indicate that JAK signaling contributes to germline cyst breakdown and primordial follicle formation by regulating oocyte loss and pregranulosa cell proliferation in the fetal mouse ovary. Our findings contribute to a better understanding of the molecular mechanism of mammalian folliculogenesis. The Company of Biologists Ltd 2017-12-14 /pmc/articles/PMC5827266/ /pubmed/29242197 http://dx.doi.org/10.1242/bio.029470 Text en © 2018. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Huang, Kun Wang, Ye Zhang, Tuo He, Meina Sun, Guanghong Wen, Jia Yan, Hao Cai, Han Yong, Changfu Xia, Guoliang Wang, Chao JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice |
title | JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice |
title_full | JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice |
title_fullStr | JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice |
title_full_unstemmed | JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice |
title_short | JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice |
title_sort | jak signaling regulates germline cyst breakdown and primordial follicle formation in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827266/ https://www.ncbi.nlm.nih.gov/pubmed/29242197 http://dx.doi.org/10.1242/bio.029470 |
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