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Maternal ELL3 loss-of-function leads to oocyte aneuploidy and early miscarriage

GSE268181 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/10/30 Platform GPL21103
Summary
Up to one-tenth of women experience miscarriage in their lifetime. Embryonic aneuploidy is a leading cause of infertility, miscarrage and congenital defects. Here, we identify loss-of-function variants of ELL3, a gene encoding a transcription elongation factor, from couples experienced consecutive early spontaneous miscarriages due to embryonic aneuploidy. Maternal ELL3 knockout leads to oocyte aneuploidy. Furthermore, we found that ELL3 localizes to the spindle during meiosis, and that ELL3 depletion in both mouse and human oocytes increases the incidence of meiotic spindle abnormality. Biochemically, ELL3 competes with TPX2 to interact with the microtubule motor KIF11, promoting its ATP utilization. Live imaging analysis shows that ELL3 is essential for promoting spindle elongation rate and driving chromosome movement. Our findings demonstrate that ELL3 loss-of-function variations could lead to oocyte aneuploidy and early miscarriage.
Published in
Maternal ELL3 loss-of-function leads to oocyte aneuploidy and early miscarriage
Zhu S, Xie P, Yang Y et al. · Nature structural & molecular biology 2025 · PMID 39820605 · doi:10.1038/s41594-024-01471-8
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Also filed as BioProject PRJNA1115055 and SRA study SRP509370. Searching any of these in the dataset finder brings you back here.

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