Maternal LDHB Safeguards Redox Balance and Developmental Competence During Preimplantation Embryo Cleavage

  • FASEB J. 2026 May 31;40(10):e71888. doi: 10.1096/fj.202601428R.
Tiantian Deng  1  2  3  4  5  6 ,  Yiwen Zhang  1  2  3  4  5  6 ,  Hao Tian  1  2  3  4  5  6 ,  Yuxin Xu  1  2  3  4  5  6 ,  Chuanxin Zhang  1  2  3  4  5  6 ,  Jiawei Wang  1  2  3  4  5  6 ,  Jiayin Gao  1  2  3  4  5  6 ,  Keliang Wu  1  2  3  4  5  6 ,  Boyang Liu  1  2  3  4  5  6
Affiliations
  • 1. State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China.
  • 2. Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, China.
  • 3. Shandong Key Laboratory of Reproductive Health and Birth Defects Prevention and Control, Jinan, Shandong, China.
  • 4. Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China.
  • 5. Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China.
  • 6. Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences, Jinan, Shandong, China.
PMID: 42117986 DOI: 10.1096/fj.202601428R
Abstract

The metabolic regulation in embryos is distinct from that in somatic cells. Early mammalian embryos obtain nutrients from the maternal environment to fulfill the energy requirements of growth and development, and lactate is one of the major substrates of embryonic energy metabolism. To interrogate metabolic regulation during early embryogenesis, we transiently inhibited maternally supplied Lactate Dehydrogenase B (LDHB) in early embryos, and found that inhibition led to developmental arrest during the 4- to 8-cell transition, reduced ATP levels, impaired mitochondrial readouts and a decreased NAD+/NADH ratio. Aspartate supplementation rescued developmental progression and restored the NAD+/NADH balance in a malate-aspartate shuttle (MAS)-dependent manner. Together, these data suggest that maternal LDHB is important during the 4- to 8-cell transition to maintain LDH-linked redox homeostasis, and that MAS activity contributes to redox restoration during the rescue. Our study highlights a link between metabolic flexibility, redox homeostasis, and developmental competence during mammalian preimplantation development.

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