Genomic Factors Influencing Male Fertility Traits

Male fertility is governed by a complex interplay of genetic variants that influence sperm production, morphology and function. Genome‐wide association studies have revealed that semen quality parameters such as sperm concentration, motility and morphology are highly polygenic, with heritabilities ranging from low to moderate. Quantitative trait loci underlying fertility traits often map to regions enriched for genes involved in spermatogenesis, testis development and sperm‐egg interaction. Expression quantitative trait loci and transcriptome profiling across testis and epididymal tissues have further highlighted regulatory variants that modulate gene expression and splicing of key fertility genes. Several candidate genes, including those encoding structural sperm proteins, ion channels and signalling molecules, show conserved roles across mammals. X‐chromosome loci also contribute substantially to variation in male fertility but have been understudied in routine analyses. Insights gained from livestock models, especially cattle and pigs, inform human reproductive biology and underpin marker‐assisted selection strategies aimed at improving reproductive efficiency in both agricultural and clinical settings.

Research from Nature Portfolio

A large‐scale study of mature bulls characterised gene expression and splicing variation in testis, epididymis and vas deferens and associated over 400 000 molecular phenotypes with genome‐wide variants. This work uncovered tens of thousands of regulatory loci, demonstrated pronounced transcriptional complexity in testicular tissue and identified key genes (for example WDR19, SPATA16 and KCTD19) whose expression mediates quantitative fertility variation. In a foundational genome‐wide association analysis of crossbred beef bulls, windows explaining more than 1 per cent of the genetic variance for scrotal circumference and sperm motility were mapped, yielding positional candidate genes such as MAP3K1, VIP and SOD2 that prioritise biological pathways for further functional investigation.

Genomic Factors Influencing Male Fertility Traits publication trend

The graph below shows the total number of articles in genomic factors influencing male fertility traits across all publications each year (not limited to Nature Index journals).

Technical terms

Genome‐wide association study (GWAS): Analysis that scans markers across the genome to find variants associated with quantitative traits.

Quantitative trait locus (QTL): A genomic region that contributes to variation in a quantitative phenotype such as sperm motility.

Single nucleotide polymorphism (SNP): A single base‐pair variation in the genome used as a marker for genetic studies.

Heritability: The proportion of phenotypic variance in a trait attributable to genetic differences within a population.

Expression quantitative trait locus (eQTL): A genomic locus where genetic variation influences gene expression levels.

References

1. Molecular quantitative trait loci in reproductive tissues impact male fertility in cattle. Nature Communications (2024).
2. Determinant genetic markers of semen quality in livestock. Frontiers in Endocrinology (2024).
3. Sequence level genome-wide associations for bull production and fertility traits in tropically adapted bulls. BMC Genomics (2023).
4. Genome-wide association study to identify genomic regions and positional candidate genes associated with male fertility in beef cattle. Scientific Reports (2020).