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      Growth differentiation factor-9 is required during early ovarian folliculogenesis.

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

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          Abstract

          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.

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