Mitofusin1 in oocyte is essential for female fertility

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 ( Mfn1 fl/fl ;Zp3-Cre or Mfn2 fl/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 Mfn1 fl/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 Mfn1 fl/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.