Abstract
Mitofusins (Mfn) are the important regulators of mitochondrial organization in mammalian cells; however, their roles during oocyte development remain unknown. In the present study, we generated mice with oocyte-specific knockout of Mfn1 or Mfn2 (Mfn1fl/fl;Zp3-Cre or Mfn2fl/fl;Zp3-Cre). We report that deletion of Mfn1, but not Mfn2, in oocytes leads to female mice sterility, associated with the defective folliculogenesis and impaired oocyte quality. In specific, follicles are arrested at secondary stage in Mfn1fl/fl;Zp3-Cre mice, accompanying with the reduced proliferation of granulosa cells. Moreover, alterations of mitochondrial structure and distribution pattern are readily observed in Mfn1-null oocytes. Consistent with this, mitochondrial activity and function are severely disrupted in oocytes from Mfn1fl/fl;Zp3-Cre mice. In addition, the differentially expressed genes in Mfn1-deleted oocytes are also identified by whole-transcriptome sequencing. In sum, these results demonstrate that Mfn1-modulated mitochondrial function is essential for oocyte development and folliculogenesis, providing a novel mechanism determining female fertility.