ER stress-associated IRE1α signalling links impaired QPRT-dependent NAD⁺ biosynthesis to reduced oocyte competence

IRE1α-linked ER stress is associated with reduced QPRT-dependent NAD⁺ biosynthesis, and NMN restores NAD levels and improves meiotic maturation in poor-grade goat oocytes.

• Why it matters: Natural differences in oocyte quality are tied to metabolic and organelle balance, but how ER stress reshapes NAD biosynthesis and oocyte competence is unclear.
• What they did: Poor-grade goat oocytes showed profound NAD depletion, quinolinic acid accumulation, and reduced QPRT expression; QPRT restoration or bypass improved meiotic maturation, while IRE1-associated activity reduced QPRT RNA stability and processed QPRT RNA in vitro.
• The result: NMN supplementation restored NAD levels and improved calcium homeostasis, oxidative stress, mitochondrial membrane potential, and early embryonic development, with benefits linked to SIRT6 activity and DNA methylation-associated fluorescence, and it improved meiotic maturation in poor-grade bovine and porcine oocytes.

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