mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.

We have shown that inhibition of mTOR in granulosa cells and ovarian follicles results in compromised granulosa proliferation and reduced follicle growth. Further analysis here using spontaneously immortalized rat granulosa cells has revealed that mTOR pathway activity is enhanced during M-phase of...

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Autores principales:	James Yu, Aylin Yaba, Corinna Kasiman, Travis Thomson, Joshua Johnson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc05792698d94dc49e741e344181fce6
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spelling	oai:doaj.org-article:fc05792698d94dc49e741e344181fce62021-11-18T06:50:45ZmTOR controls ovarian follicle growth by regulating granulosa cell proliferation.1932-620310.1371/journal.pone.0021415https://doaj.org/article/fc05792698d94dc49e741e344181fce62011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21750711/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203We have shown that inhibition of mTOR in granulosa cells and ovarian follicles results in compromised granulosa proliferation and reduced follicle growth. Further analysis here using spontaneously immortalized rat granulosa cells has revealed that mTOR pathway activity is enhanced during M-phase of the cell cycle. mTOR specific phosphorylation of p70S6 kinase and 4E-BP, and expression of Raptor are all enhanced during M-phase. The predominant effect of mTOR inhibition by the specific inhibitor Rapamycin (RAP) was a dose-responsive arrest in the G1 cell cycle stage. The fraction of granulosa cells that continued to divide in the presence of RAP exhibited a dose-dependent increase in aberrant mitotic figures known as anaphase bridges. Strikingly, estradiol consistently decreased the incidence of aberrant mitotic figures. In mice treated with RAP, the mitotic index was reduced compared to controls, and a similar increase in aberrant mitotic events was noted. RAP injected during a superovulation regime resulted in a dose-dependent reduction in the numbers of eggs ovulated. Implications for the real-time regulation of follicle growth and dominance, including the consequences of increased numbers of aneuploid granulosa cells, are discussed.James YuAylin YabaCorinna KasimanTravis ThomsonJoshua JohnsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e21415 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q James Yu Aylin Yaba Corinna Kasiman Travis Thomson Joshua Johnson mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.
description	We have shown that inhibition of mTOR in granulosa cells and ovarian follicles results in compromised granulosa proliferation and reduced follicle growth. Further analysis here using spontaneously immortalized rat granulosa cells has revealed that mTOR pathway activity is enhanced during M-phase of the cell cycle. mTOR specific phosphorylation of p70S6 kinase and 4E-BP, and expression of Raptor are all enhanced during M-phase. The predominant effect of mTOR inhibition by the specific inhibitor Rapamycin (RAP) was a dose-responsive arrest in the G1 cell cycle stage. The fraction of granulosa cells that continued to divide in the presence of RAP exhibited a dose-dependent increase in aberrant mitotic figures known as anaphase bridges. Strikingly, estradiol consistently decreased the incidence of aberrant mitotic figures. In mice treated with RAP, the mitotic index was reduced compared to controls, and a similar increase in aberrant mitotic events was noted. RAP injected during a superovulation regime resulted in a dose-dependent reduction in the numbers of eggs ovulated. Implications for the real-time regulation of follicle growth and dominance, including the consequences of increased numbers of aneuploid granulosa cells, are discussed.
format	article
author	James Yu Aylin Yaba Corinna Kasiman Travis Thomson Joshua Johnson
author_facet	James Yu Aylin Yaba Corinna Kasiman Travis Thomson Joshua Johnson
author_sort	James Yu
title	mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.
title_short	mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.
title_full	mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.
title_fullStr	mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.
title_full_unstemmed	mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.
title_sort	mtor controls ovarian follicle growth by regulating granulosa cell proliferation.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/fc05792698d94dc49e741e344181fce6
work_keys_str_mv	AT jamesyu mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation AT aylinyaba mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation AT corinnakasiman mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation AT travisthomson mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation AT joshuajohnson mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation
_version_	1718424331194728448

mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.

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