Growth differentiation factor-9 is required during early ovarian folliculogenesis.
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.
Dong
J
J
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Albertini
D F
DF
Nishimori
K
K
Kumar
T R
TR
Lu
N
N
Matzuk
M M
MM
D000818:Animals; D055430:Bone Morphogenetic Protein 15; D002454:Cell Differentiation; D002460:Cell Line; D005260:Female; D005497:Follicular Cyst / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D018390:Gene Targeting; D055429:Growth Differentiation Factor 9; D006133:Growth Substances / Q000235:genetics / Q000502:physiology*; D007247:Infertility, Female / Q000235:genetics / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D006080:Ovarian Follicle / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000473:pathology / Q000502:physiology*
C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins