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1 Mitofusin 1 is required for the oocyte-granulosa cell communication that 1 regulates oogenesis 2 3 Thiago S SUMMARY 21Mitochondrial function, largely regulated by the dynamics of this organelle, is 22 inextricably linked to oocyte health. While the proteins that modulate 23 mitochondrial fusion, Mitofusin 1 (MFN1) and 2 (MFN2), are required for 24 embryogenesis, their role in oocyte development remains unclear. Here we 25show that the oocyte-specific deletion of Mfn1, but not Mfn2, results in a 26 complete loss of oocyte growth and ovulation due to a block in folliculogenesis 27 at the preantral-to-antral follicle transition. We pinpoint the loss of oocyte 28 ovulation to disrupted oocyte-somatic cell communication -Mfn1-null oocytes 29 are deficient for the production of the important somatic cell signaling factor 30 GDF9. Unexpectedly, the double loss of Mfn1 and Mfn2 mitigates the effects 31 on oocyte growth and ovulation, which is explained by a partial rescue of 32 oocyte-somatic cell communication and folliculogenesis. Together, this work 33 demonstrates that mitochondrial function influences communication of oocyte 34 with follicular somatic cells and suggests that the balanced expression of 35 modulators of mitochondrial dynamics is critical for proper oocyte development. 36Keywords: folliculogenesis, oocyte, mitochondria, mtDNA, fusion, mitofusin, 37 MFN1, MFN2, GDF9. 38 the rate of first polar body (PB1) extrusion, a readout for meiotic progression 130 to the metaphase-II stage. Only 3.1% of the oocytes that were ovulated by 131Mfn1&2-cKO mice contained PB1 ( Figure 1D), while 61.4% of them were 132 arrested at the GV stage. This finding was confirmed by in vitro maturation of 133 GV oocytes ( Figures 1E and 1F), indicating that Mfn1&2-cKO females were 134 infertile due to ovulation of unviable oocytes. Mating of superovulated 135Mfn1&2-cKO females with WT males also confirmed this as the ovulated 136 oocytes were not fertilized (data not show). The consequence of Mfn1 137