Loss of inhibin alpha uncouples oocyte-granulosa cell dynamics and disrupts postnatal folliculogenesis

Dev Biol. 2009 Oct 15;334(2):458-67. doi: 10.1016/j.ydbio.2009.08.001. Epub 2009 Aug 8.


Targeted disruption of the inhibin alpha gene (Inha(-)(/)(-)) in mice results in an ovarian phenotype of granulosa cell tumors that renders the animals infertile. Little is known about the reproductive defects prior to tumor development. Here, we report novel data on early follicle dynamics in Inha(-)(/)(-) mice, which demonstrate that inhibin alpha has important consequences upon follicle development. Morphological changes in both germ and somatic cells were evident in postnatal day 12 ovaries, with Inha(-/-) mice exhibiting numerous multilayered follicles that were far more advanced than those observed in age-matched controls. These changes were accompanied by alterations in follicle dynamics such that Inha(-/-) ovaries had fewer follicles in the resting pool and more committed in the growth phase. Absence of inhibin alpha resulted in advanced follicular maturation as marked by premature loss of anti-Müllerian hormone (AMH) in secondary follicles. Additionally, gene expression analysis revealed changes in factors known to be vital for oocyte and follicle development. Together, these data provide key evidence to suggest that regulation of the inhibin/activin system is essential for early folliculogenesis in the prepubertal mouse ovary.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Aromatase / biosynthesis
  • Aromatase / genetics
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics
  • Female
  • Follicle Stimulating Hormone / blood
  • Gene Expression Regulation
  • Granulosa Cell Tumor / genetics*
  • Granulosa Cell Tumor / pathology
  • Granulosa Cells / pathology*
  • Inhibins / deficiency*
  • Inhibins / genetics
  • Inhibins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oocytes / pathology*
  • Ovarian Follicle / pathology*
  • Ovarian Follicle / physiopathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Receptors, FSH / biosynthesis
  • Receptors, FSH / genetics
  • Sexual Maturation


  • Cell Cycle Proteins
  • Receptors, FSH
  • inhibin-alpha subunit
  • Inhibins
  • Follicle Stimulating Hormone
  • Aromatase