{
  "abstract": "Oocyte quality is closely linked to metabolic and organelle homeostasis, but the mechanisms underlying naturally occurring differences in oocyte quality remain incompletely understood. Here, we identify a link between endoplasmic reticulum (ER) stress, impaired NAD biosynthesis and poor oocyte quality. Poor-grade goat oocytes exhibited profound NAD depletion, accompanied by quinolinic acid accumulation and reduced expression of quinolinate phosphoribosyltransferase (QPRT), suggesting a bottleneck in de novo NAD biosynthesis. Restoring QPRT expression or bypassing this metabolic step improved meiotic maturation. Further analyses revealed altered ER stress signalling, increased IRE1-associated activity and reduced QPRT RNA stability. Recombinant IRE1 processed QPRT RNA in vitro, suggesting a possible link between IRE1 activity and QPRT transcript regulation. Supplementation with nicotinamide mononucleotide (NMN) restored NAD levels and improved several features of poor-quality oocytes, including calcium homeostasis, oxidative stress and mitochondrial membrane potential. NMN treatment also improved early embryonic development, with its beneficial effects involving SIRT6 activity and changes in DNA methylation-associated fluorescence. Importantly, NMN supplementation improved meiotic maturation in poor-grade bovine and porcine oocytes, indicating that this metabolic intervention may have broader relevance across mammals. Analysis of published human oocyte proteomic data further revealed age-associated changes in ER proteostasis and NAD-related proteins. Together, our findings identify ER stress-associated disruption of QPRT-dependent NAD biosynthesis as a potential contributor to poor oocyte quality and suggest that restoring NAD metabolism may offer a strategy to improve the functional properties of compromised oocytes.",
  "abstract_shown": true,
  "affiliations": [
    "National Institute of Animal Biotechnology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "M. Athar"
    },
    {
      "name": "A. K. E"
    },
    {
      "name": "P. Birajdar"
    },
    {
      "name": "R. M"
    },
    {
      "name": "A. Kumar"
    },
    {
      "name": "A. Kumari"
    },
    {
      "name": "S. Sabnam"
    },
    {
      "name": "A. Verma"
    },
    {
      "name": "P. L"
    },
    {
      "name": "P. S. Nial"
    },
    {
      "name": "T. S. G"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Prasada Rao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9wkptrmgnaq09.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.04.764453",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764453v1.full",
  "id": "9wkptrmgnaq09",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764453v1",
  "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",
      "cell biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764453v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9wkptrmgnaq09.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:00Z",
      "native_id": "10.64898/2026.11.04.764453",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.04.764453v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "ER stress-associated IRE1α signalling links impaired QPRT-dependent NAD⁺ biosynthesis to reduced oocyte competence",
  "title_text": "ER stress-associated IRE1α signalling links impaired QPRT-dependent NAD⁺ biosynthesis to reduced oocyte competence",
  "type": "preprint",
  "updated_at": "2026-11-06T12:21:00Z",
  "url": "https://research.draconitic.com/paper/9wkptrmgnaq09",
  "venue": "bioRxiv",
  "versions": []
}