Fine-tuned programming of placenta trophoblast determines optimal maternal-fetal nutrient allocation.

Yan-Ling Wang, Amanda N Sferruzzi-Perri, Qianqian Li, Xin Yu, Xuan Shao

Journal: Current opinion in genetics & development 2025;91():102305

PMID: 39827578

Abstract

Maternal health and fetal survival during pregnancy encapsulate a paradox of cooperation and competition. One particularly intriguing aspect of this paradox involves the optimal allocation of nutrients between the mother and fetus. Despite this, the precise mechanisms governing nutrient allocation remain elusive. This review aims to provide a summation of latest research that is improving our understanding of placental metabolism and nutrient allocation between the mother and the fetus. It highlights that in addition to transporter-mediated processes for glucose, fatty acid, and amino acid transport, the human placental trophoblast utilizes a unique macropinocytosis strategy to uptake large molecules from maternal circulation in conditions of nutrient stress. In addition, placental trophoblasts undergo intensive metabolic programming and post-translational modifications during the differentiation process, which regulate trophoblast cell fate, function, and pregnancy outcomes. A number of imprinted genes have been identified to play crucial roles in balancing allocation between the mother and the fetus, yet their role in trophoblast macropinocytosis and metabolic reprogramming requires study. Further work in this area of placental nutrient allocation is essential for identifying the pathogenesis of pregnancy disorders and developing novel therapeutic interventions.

Address: State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.; State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.; State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: [email protected].; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdoms. Electronic address: [email protected].; State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: [email protected].

DOI: 10.1016/j.gde.2024.102305

MeSH Terms: Humans, Pregnancy, Female, Trophoblasts, Placenta, Maternal-Fetal Exchange, Nutrients, Fetus