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Impaired Sperm Motility are Linked to Reduced Meiotic Crossover Rates
23 Pages Posted: 17 Dec 2024
More...Abstract
Impaired sperm motility is a common clinical indicator for diagnosing male infertility, yet the genetic factors underlying this pathological phenotype remain poorly understood. Our study demonstrates that comparative analysis of genome sequences derived from diploid somatic cells and a few single haploid sperm cells of males is sufficient to identify genetic abnormalities associated with reduced sperm motility. In individuals with asthenospermia, a condition characterized by impaired sperm motility, we identify a significantly reduced rate of meiotic crossing over, a critical step in spermatogenesis that facilitates DNA exchange between maternal and paternal chromosome pairs. Additionally, we find that crossing over frequencies decrease with age in both normal and asthenospermia males, contributing to reduced fertility. A genome-wide association study identifies 119 genes associated with energy metabolism and DNA-related activities crucial to crossing over and meiosis. Altered expression of identified genes, including SPATA18, a known crucial regulator of spermatogenesis, is validated by transcriptome analysis of an independent cohort. Our findings highlight a strong link between crossing over, sperm motility, and fertility. Furthermore, we establish a cost-effective methodology that can be used to clinically monitor the efficacy of asthenospermia treatments and can also be applied to study females, where sequencing numerous eggs is impractical.
Keywords: aneuploidy, crossing over, cellular energy deficiency, genome-wide association study, meiosis, single sperm cell sequencing
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