Cargando…
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...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130037/ https://www.ncbi.nlm.nih.gov/pubmed/21750711 http://dx.doi.org/10.1371/journal.pone.0021415 |
_version_ | 1782207577080201216 |
---|---|
author | Yu, James Yaba, Aylin Kasiman, Corinna Thomson, Travis Johnson, Joshua |
author_facet | Yu, James Yaba, Aylin Kasiman, Corinna Thomson, Travis Johnson, Joshua |
author_sort | Yu, James |
collection | PubMed |
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 | Online Article Text |
id | pubmed-3130037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31300372011-07-12 mTOR Controls Ovarian Follicle Growth by Regulating Granulosa Cell Proliferation Yu, James Yaba, Aylin Kasiman, Corinna Thomson, Travis Johnson, Joshua PLoS One Research Article 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. Public Library of Science 2011-07-05 /pmc/articles/PMC3130037/ /pubmed/21750711 http://dx.doi.org/10.1371/journal.pone.0021415 Text en Yu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yu, James Yaba, Aylin Kasiman, Corinna Thomson, Travis Johnson, Joshua mTOR Controls Ovarian Follicle Growth by Regulating Granulosa Cell Proliferation |
title | 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_short | mTOR Controls Ovarian Follicle Growth by Regulating Granulosa Cell Proliferation |
title_sort | mtor controls ovarian follicle growth by regulating granulosa cell proliferation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130037/ https://www.ncbi.nlm.nih.gov/pubmed/21750711 http://dx.doi.org/10.1371/journal.pone.0021415 |
work_keys_str_mv | AT yujames mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation AT yabaaylin mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation AT kasimancorinna mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation AT thomsontravis mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation AT johnsonjoshua mtorcontrolsovarianfolliclegrowthbyregulatinggranulosacellproliferation |