Throughout the development of ovarian follicles, the oocyte increases 300-fold in volume and the surrounding granulosa cells undergo differentiation and proliferation. There is a constant cross-talk between the oocyte and the surrounding granulosa cells during folliculogenesis, however, how mitochondrial functions in oocyte is linked to follicle development remains poorly understood. During oocyte growth there is a dramatic increase in mitochondrial biogenesis resulting in an increase from around 1,000 to 200,000 mitochondria. Mitochondrial biogenesis requires mtDNA replication, largely driven by Transcription Factor A, Mitochondrial (TFAM) and mitochondrial fission, primarily driven by Dynamin-related Protein 1 (DRP1). Oocytes and their granulosa cells are in constant cross-talk via gap-junctions and it is essential for normal follicle and oocyte development. Mitochondrial function is largely regarded as cell autonomous, but it is unclear how compromised mitochondrial function in one cell type, the oocyte, may influence the development of the entire follicular compartment. We have addressed this question by examining follicular development in oocyte-specific knock-outs of Drp1 and Tfam.
Targeted deletion of either Drp1 or Tfam from primordial follicle oocytes does not significantly affect the folliculogenesis and production of fully-grown oocytes in prepubertal mice. However, around the time of puberty in both models, folliculogenesis is severely disrupted with a follicular arrest at primary and secondary stages. This mirrors other models in which oocyte-somatic cell communication is disrupted. Transcriptional analysis of TFAM and DRP1-deleted oocytes reveals that mitochondrial function in oocytes has key roles in regulating the levels of the regulators of the cellular inflammatory response. In conclusion, our results show that disrupting oocyte mitochondrial function has an extended phenotype beyond the oocyte that impacts the entire follicle at a specific stage of development. The precise mechanism of this effect requires further investigation but may involve disrupted oocyte-somatic cell communication accompanied by an upregulation of inflammatory signalling.