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<p>Maternal metabolic stress is a major determinant of progeny health and disease susceptibility, yet the mechanisms linking germline metabolism to lifelong changes in tissue physiology remain poorly defined. Here, we show that maternal metabolic stress alters the cellular composition of the progeny intestinal epithelium through a conserved metabolic pathway. Germline metabolic dysfunction depletes NAD⁺ in mature oocytes, reprogramming progeny redox metabolism and impairing the methionine cycle. This metabolic shift reduces protein levels of the <i>Notch</i> ligand <i>Delta</i>, disrupting intestinal stem cell niche signaling and altering progeny intestinal physiology. Across insect and mammalian models, our findings reveal that maternal metabolic health has conserved effects on progeny metabolism and intestinal function. Together, this work identifies heritable redox-metabolic changes as a mechanistic link between maternal metabolic stress, stem cell regulation, and intestinal disease susceptibility.</p>

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Maternal metabolic stress regulates progeny intestinal stem cell niche signaling through heritable changes in redox metabolites

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月3日

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  • Helin Hocaoglu,
  • Shenlu Qin,
  • Leah Eller,
  • Farhan Abu,
  • Benjamin Ohlstein,
  • Lei Wang,
  • Matthew H. Sieber

摘要

Maternal metabolic stress is a major determinant of progeny health and disease susceptibility, yet the mechanisms linking germline metabolism to lifelong changes in tissue physiology remain poorly defined. Here, we show that maternal metabolic stress alters the cellular composition of the progeny intestinal epithelium through a conserved metabolic pathway. Germline metabolic dysfunction depletes NAD⁺ in mature oocytes, reprogramming progeny redox metabolism and impairing the methionine cycle. This metabolic shift reduces protein levels of the Notch ligand Delta, disrupting intestinal stem cell niche signaling and altering progeny intestinal physiology. Across insect and mammalian models, our findings reveal that maternal metabolic health has conserved effects on progeny metabolism and intestinal function. Together, this work identifies heritable redox-metabolic changes as a mechanistic link between maternal metabolic stress, stem cell regulation, and intestinal disease susceptibility.