ArticlebioRxiv : the preprint server for biology2026
Sperm AluY Epimutations in Male Partners of Couples with Unexplained Recurrent Pregnancy Loss.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Recurrent pregnancy loss (RPL) affects 5% of couples worldwide. Over half of cases remain unexplained (uRPL) as paternal factors are rarely clinically evaluated or studied. This study presents data showing that sperm DNA methylation is a putative contributor to RPL. Using ONT direct whole methylome sequencing, we generated the largest cohort of locus-resolved, single-molecule sperm methylome maps from men with uRPL. We identified 294 differentially methylated regions (DMRs), of which 158 (53.7%) overlapped AluY repetitive elements, representing significant enrichment (z=40.9); most were hypomethylated in uRPL sperm and spanned the full length of individual AluY insertions. Because of single-molecule resolution, we show that the methylation differences found in uRPL sperm occur in a subpopulation of sperm rather than a uniform DNA methylation change across all sperm. AluY epimutation represents a previously unrecognized, predominant signature of paternal epigenetic perturbation in uRPL, establishing repetitive elements as a new axis of sperm epigenetic risk.
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