CPEB3 deficiency in mice affect ovarian follicle development and causes premature ovarian insufficiency

Cell Death Dis. 2021 Dec 20;13(1):21. doi: 10.1038/s41419-021-04374-4.


Premature ovarian insufficiency (POI) is a heterogeneous and multifactorial disorder. In recent years, there has been an increasing interest in research on the pathogenesis and treatment of POI, owing to the implementation of the second-child policy in China. Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is an RNA-binding protein that can bind to specific RNA sequences. CPEB3 can bind to and affect the expression, cellular location, and stability of target RNAs. Cpeb3 is highly expressed in the ovary; however, its functions remain unknown. In this study, Cpeb3-mutant mice were used to characterize the physiological functions of CPEB3. Cpeb3-mutant female mice manifested signs of gradual loss of ovarian follicles, ovarian follicle development arrest, increased follicle atresia, and subfertility with a phenotype analogous to POI in women. Further analysis showed that granulosa cell proliferation was inhibited and apoptosis was markedly increased in Cpeb3-mutant ovaries. In addition, the expression of Gdf9, a potential target of CPEB3, was decreased in Cpeb3-mutant ovaries and oocytes. Altogether, these results reveal that CPEB3 is essential for ovarian follicle development and female fertility as it regulates the expression of Gdf9 in oocytes, disruption of which leads to impaired ovarian follicle development and POI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • CRISPR-Cas Systems
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Female
  • Fertility / genetics*
  • Granulosa Cells / metabolism*
  • Growth Differentiation Factor 9 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation*
  • Oocytes / metabolism
  • Phenotype
  • Pregnancy
  • Primary Ovarian Insufficiency / genetics
  • Primary Ovarian Insufficiency / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / genetics*


  • Cpeb3 protein, mouse
  • Gdf9 protein, mouse
  • Growth Differentiation Factor 9
  • RNA-Binding Proteins