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  • Adhikari, DeepakUmeå universitet,Institutionen för medicinsk kemi och biofysik (author)

Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles

  • Article/chapterEnglish2010

Publisher, publication year, extent ...

  • 2009-10-20
  • Oxford University Press (OUP),2010
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-42927
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-42927URI
  • https://doi.org/10.1093/hmg/ddp483DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • To maintain the female reproductive lifespan, the majority of ovarian primordial follicles are preserved in a quiescent state in order to provide ova for later reproductive life. However, the molecular mechanism that maintains the long quiescence of primordial follicles is poorly understood. Here we provide genetic evidence to show that the tumor suppressor tuberous sclerosis complex 1 (Tsc1), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the quiescence of primordial follicles. In mutant mice lacking the Tsc1 gene in oocytes, the entire pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in the oocyte, ending up with follicular depletion in early adulthood and causing premature ovarian failure (POF). We further show that maintenance of the quiescence of primordial follicles requires synergistic, collaborative functioning of both Tsc and PTEN (phosphatase and tensin homolog deleted on chromosome 10) and that these two molecules suppress follicular activation through distinct ways. Our results suggest that Tsc/mTORC1 signaling and PTEN/PI3K (phosphatidylinositol 3 kinase) signaling synergistically regulate the dormancy and activation of primordial follicles, and together ensure the proper length of female reproductive life. Deregulation of these signaling pathways in oocytes results in pathological conditions of the ovary, including POF and infertility.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Zheng, WenjingUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)wezh0004 (author)
  • Shen, YanUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)yush0002 (author)
  • Gorre, NagarajuUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)gona0003 (author)
  • Hämäläinen, Tuula (author)
  • Cooney, Austin J (author)
  • Huhtaniemi, Ilpo (author)
  • Lan, Zi-Jian (author)
  • Liu, KuiUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)kuli0001 (author)
  • Umeå universitetInstitutionen för medicinsk kemi och biofysik (creator_code:org_t)

Related titles

  • In:Human Molecular Genetics: Oxford University Press (OUP)19:3, s. 397-4100964-69061460-2083

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