Species: mouse
Mutation name:
type: null mutation
fertility: subfertile
Comment: CHTF18 ensures the quantity and quality of the ovarian reserve†. Holton RA et al. (2020) The number and quality of oocytes, as well as the decline in both of these parameters with age, determines reproductive potential in women. However, the underlying mechanisms of this diminution are incompletely understood. Previously, we identified novel roles for CHTF18 (Chromosome Transmission Fidelity Factor 18), a component of the conserved Replication Factor C-like complex, in male fertility and gametogenesis. Currently, we reveal crucial roles for CHTF18 in female meiosis and oocyte development. Chtf18-/- female mice are subfertile and have fewer offspring beginning at 6 months of age. Consistent with age-dependent subfertility, Chtf18-/- ovaries contain fewer ovarian follicles at all stages of follicle development, but the decreases are more significant at three and six months of age. By six months of age there are marked reductions of both primordial and growing ovarian follicle pools in Chtf18-/- females. Chromosomal synapsis in Chtf18-/- oocytes is complete but meiotic recombination is impaired resulting in increased DNA double-strand breaks and fewer DNA crossovers, and early homolog disjunction during meiosis I. Consistent with poor oocyte quality, the majority of Chtf18-/- oocytes fail to progress to metaphase II following meiotic resumption and a significant percentage of those that do progress are aneuploid. Collectively, our findings indicate critical functions for CHTF18 in ensuring both the quantity and quality of the mammalian oocyte pool.//////////////////