Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Kun, Wang, Ye, Zhang, Tuo, He, Meina, Sun, Guanghong, Wen, Jia, Yan, Hao, Cai, Han, Yong, Changfu, Xia, Guoliang, Wang, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2017
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
_version_ 1783302448008396800
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
work_keys_str_mv AT huangkun jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT wangye jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT zhangtuo jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT hemeina jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT sunguanghong jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT wenjia jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT yanhao jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT caihan jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT yongchangfu jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT xiaguoliang jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice
AT wangchao jaksignalingregulatesgermlinecystbreakdownandprimordialfollicleformationinmice