{
  "abstract": "Recurrent pregnancy loss (RPL) affects 5% of couples worldwide. Over half of cases remain unexplained (uRPL), in part because paternal factors are rarely evaluated beyond paternal karyotype. Sperm DNA methylation is a putative paternal contributor to RPL. Using ONT direct whole methylome sequencing, we generated the first and largest cohort of locus-resolved, single-molecule sperm methylome maps from men with uRPL to date (n=39). 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. Affected loci were underrepresented for imprinting-associated chromatin marks and instead overrepresented for H2A.Z. Although DMR-associated genes were enriched for neuronal GO terms, many converge on reported roles in implantation, placentation, and early embryonic development. 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.",
  "abstract_shown": true,
  "affiliations": [
    "UT Health San Antonio"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "E. Kamaraj"
    },
    {
      "name": "J. Moore"
    },
    {
      "name": "M. Keni"
    },
    {
      "name": "A. Terry"
    },
    {
      "name": "N. Salehisedeh"
    },
    {
      "name": "N. Biju"
    },
    {
      "name": "M. Susiarjo"
    },
    {
      "name": "J. T. Hill"
    },
    {
      "name": "T. Jenkins"
    },
    {
      "affs": [
        0
      ],
      "name": "W. mak"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4ah9mjr11ppb0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.753615",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753615v1.full",
  "id": "4ah9mjr11ppb0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753615v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "developmental biology"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7214292234",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753615v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4ah9mjr11ppb0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:32Z",
      "native_id": "10.64898/2026.09.24.753615",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.753615v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:developmental biology",
      "subfield": "developmental-biology"
    }
  ],
  "title": "Sperm AluY Epimutations in Male Partners of Couples with Unexplained Recurrent Pregnancy Loss",
  "title_text": "Sperm AluY Epimutations in Male Partners of Couples with Unexplained Recurrent Pregnancy Loss",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:32Z",
  "url": "https://research.draconitic.com/paper/4ah9mjr11ppb0",
  "venue": "bioRxiv",
  "versions": []
}