Regulation of maternal-fetal metabolic communication

Cell Mol Life Sci. 2021 Feb;78(4):1455-1486. doi: 10.1007/s00018-020-03674-w. Epub 2020 Oct 21.


Pregnancy may be the most nutritionally sensitive stage in the life cycle, and improved metabolic health during gestation and early postnatal life can reduce the risk of chronic disease in adulthood. Successful pregnancy requires coordinated metabolic, hormonal, and immunological communication. In this review, maternal-fetal metabolic communication is defined as the bidirectional communication of nutritional status and metabolic demand by various modes including circulating metabolites, endocrine molecules, and other secreted factors. Emphasis is placed on metabolites as a means of maternal-fetal communication by synthesizing findings from studies in humans, non-human primates, domestic animals, rabbits, and rodents. In this review, fetal, placental, and maternal metabolic adaptations are discussed in turn. (1) Fetal macronutrient needs are summarized in terms of the physiological adaptations in place to ensure their proper allocation. (2) Placental metabolite transport and maternal physiological adaptations during gestation, including changes in energy budget, are also discussed. (3) Maternal nutrient limitation and metabolic disorders of pregnancy serve as case studies of the dynamic nature of maternal-fetal metabolic communication. The review concludes with a summary of recent research efforts to identify metabolites, endocrine molecules, and other secreted factors that mediate this communication, with particular emphasis on serum/plasma metabolomics in humans, non-human primates, and rodents. A better understanding of maternal-fetal metabolic communication in health and disease may reveal novel biomarkers and therapeutic targets for metabolic disorders of pregnancy.

Keywords: Biomarkers; Fetal metabolism; Maternal–fetal; Metabolomics; Placenta; Pregnancy.

Publication types

  • Review

MeSH terms

  • Animals
  • Female
  • Fetal Development / genetics*
  • Fetus / metabolism*
  • Humans
  • Maternal-Fetal Exchange / genetics*
  • Maternal-Fetal Exchange / physiology
  • Metabolome / genetics*
  • Metabolomics
  • Placenta / metabolism
  • Pregnancy
  • Rabbits