Journal article
CHTF18 ensures the quantity and quality of the ovarian reserve
Biology of reproduction, v 103(1)
27 Mar 2020
PMID: 32219340
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 follicles at all stages of folliculogenesis than wild type ovaries, but the decreases are more significant at 3 and 6 months of age. By 6 months of age, both primordial and growing ovarian follicle pools are markedly reduced to near depletion. Chromosomal synapsis in Chtf18–/– oocytes is complete, but meiotic recombination is impaired resulting in persistent DNA double-strand breaks, fewer 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. Summary sentence CHTF18 ensures both the quantity and quality of the mammalian oocyte pool and may play a role in delaying ovarian aging.
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Details
- Title
- CHTF18 ensures the quantity and quality of the ovarian reserve
- Creators
- Rebecca A Holton - Department of Biochemistry and Molecular BiologyAbigail M Harris - Department of Biochemistry and Molecular BiologyBarenya Mukerji - Department of Biochemistry and Molecular BiologyTanu Singh - Department of Biochemistry and Molecular BiologyFerdusy Dia - Department of Biochemistry and Molecular BiologyKaren M Berkowitz - Drexel University
- Publication Details
- Biology of reproduction, v 103(1)
- Publisher
- Society for the Study of Reproduction
- Number of pages
- 12
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000592972000006
- Scopus ID
- 2-s2.0-85087096854
- Other Identifier
- 991019168455204721
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- Web of Science research areas
- Reproductive Biology