Abstract
Mitochondria are dynamic organelles that continually adapt their structure through fusion and fission in response to changes in their bioenergetic environment. Targeted deletion of mitochondrial fusion protein mitofusin1 (MFN1) in oocytes resulted in female infertility associated with failure to achieve oocyte maturation. Oocyte-granulosa cell communication was impaired, and cadherins and connexins were downregulated, resulting in follicle developmental arrest at the secondary follicle stage. Deletion of MFN1 in oocytes resulted in mitochondrial dysfunction and altered mitochondrial dynamics, as well as accumulation of ceramide, which contributed to increased apoptosis and a reproductive phenotype that was partially rescued by treatment with ceramide synthesis inhibitor myriocin. Absence of MFN1 and resulting apoptotic cell loss also caused depletion of ovarian follicular reserve, and a phenotype consistent with accelerated female reproductive aging.