Growth differentiation factor-9 is required during early ovarian folliculogenesis

Nature. 1996 Oct 10;383(6600):531-5. doi: 10.1038/383531a0.


Growth factors synthesized by ovarian somatic cells directly affect oocyte growth and function, but it is unclear whether oocyte-secreted factors play a reciprocal role in modulating somatic cell functions in vivo. During the functional analysis of members of the transforming growth factor-beta superfamily in mouse development, we have uncovered a new family member, growth differentiation factor-9 (GDF-9), which is required for ovarian folliculogenesis. GDF-9 messenger RNA is synthesized only in the oocyte from the primary one-layer follicle stage until after ovulation. Here we analyse ovaries from GDF-9-deficient female mice and demonstrate that primordial and primary one-layer follicles can be formed, but there is a block in follicular development beyond the primary one-layer follicle stage which leads to complete infertility. Oocyte growth and zona pellucida formation proceed normally, but other aspects of oocyte differentiation are compromised. Thus, GDF-9 is the first oocyte-derived growth factor required for somatic cell function in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 15
  • Cell Differentiation
  • Cell Line
  • Female
  • Follicular Cyst / genetics
  • Follicular Cyst / pathology
  • Gene Deletion
  • Gene Targeting
  • Growth Differentiation Factor 9
  • Growth Substances / genetics
  • Growth Substances / physiology*
  • Infertility, Female / genetics
  • Infertility, Female / pathology
  • Intercellular Signaling Peptides and Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Ovarian Follicle / cytology
  • Ovarian Follicle / pathology
  • Ovarian Follicle / physiology*
  • Ovary / cytology
  • Ovary / pathology
  • Ovary / physiology*


  • Bmp15 protein, mouse
  • Bone Morphogenetic Protein 15
  • Gdf9 protein, mouse
  • Growth Differentiation Factor 9
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins