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  3. Dynamics of the Mammalian Placental Metabolome in Placentogenesis and Embryonic Development

Dynamics of the Mammalian Placental Metabolome in Placentogenesis and Embryonic Development

  • Adv Sci (Weinh). 2026 Jan 28:e07928. doi: 10.1002/advs.202507928.
Gang Chen 1 2 3,  Zichen Liu 1 2 3,  Mengyi Wei 1 2 3,  Qian Li 1 2 3,  Liang Wu 4 5,  Kunyuan Yu 1 2 3,  Yanhong Xu 1 2 3,  Dainan Yu 1 2 3,  Wenwu Ma 1 2 3,  Hongmei Wang 1 2 3,  Ng Shyh-Chang 1 2 3,  Jinglei Zhai 1 6 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, P. R. China.
  • 2 University of Chinese Academy of Sciences, Beijing, P. R. China.
  • 3 Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, P. R. China.
  • 4 Reproductive Medical Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China.
  • 5 Henan Key Laboratory of Reproduction and Genetics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China.
  • 6 Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.
PMID: 41603190 DOI: 10.1002/advs.202507928
Abstract

Mammalian placental metabolism is crucial for both placental and embryonic development. However, the metabolic profiles of placentas and their regulatory roles in placentogenesis and embryonic development at different developmental stages remain poorly characterized. To address these questions, we collect 501 mouse placentas spanning embryonic day (E) 8.5-14.5 and construct metabolomic-transcriptomic atlases of placentogenesis. Metabolomic and transcriptomic analyses reveal that placental samples from E8.5 to E14.5 are clustered into three separated states: E8.5, E9.5-10.5, and E11.5-14.5, pinpointing the metabolic transitions during placentogenesis from E8.5 to E9.5 and from E10.5 to E11.5. Based on a series of metabolite and enrichment analyses, Nicotinamide adenine dinucleotide (NAD(H)), flavin adenine dinucleotide (FAD), and L-glutamate (Glu) are identified as differentially abundant metabolites (DAMs) during E8.5-14.5. Using in vitro cultured (IVC) embryos, NAD(H) is shown to promote the extension of embryonic body length, through accelerated segmentation and increased proliferation, as verified in NAD(H)-treated mouse embryonic stem cell (mESC)-induced presomitic mesoderm (PSM)-like progenitor cells. These findings not only serve as an invaluable resource for understanding placental metabolism and its contribution to embryogenesis but also shed light on the mechanisms underlying developmental abnormalities associated with placental metabolic dysfunction.

Keywords

embryo in vitro culture; embryonic development; nicotinamide adenine dinucleotide; placenta metabolism; psm‐like progenitor cells.

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