Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy

Cesar A Perez-Ramirez; Haruko Nakano; Richard C Law; Nedas Matulionis; Jennifer Thompson; Andrew Pfeiffer; Junyoung O Park; Atsushi Nakano; Heather R Christofk

doi:10.1016/j.cell.2023.11.011

Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy

Cell. 2024 Jan 4;187(1):204-215.e14. doi: 10.1016/j.cell.2023.11.011. Epub 2023 Dec 8.

Authors

Cesar A Perez-Ramirez¹, Haruko Nakano², Richard C Law³, Nedas Matulionis⁴, Jennifer Thompson², Andrew Pfeiffer⁴, Junyoung O Park⁵, Atsushi Nakano⁶, Heather R Christofk⁷

Affiliations

¹ Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA.
² Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
³ Department of Chemical and Biomolecular Engineering, UCLA, Los Angeles, CA 90095, USA.
⁴ Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
⁵ Department of Chemical and Biomolecular Engineering, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA.
⁶ Department of Molecular, Cell, and Developmental Biology, UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: anakano@ucla.edu.
⁷ Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA. Electronic address: hchristofk@mednet.ucla.edu.

PMID: 38070508
PMCID: PMC10843853 (available on 2025-01-04)
DOI: 10.1016/j.cell.2023.11.011

Abstract

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using ¹³C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing ¹³C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations due to maternal hyperglycemia.

Keywords: development; diabetes; fetal metabolism; isotope tracing; metabolism; metabolomics; pregnancy.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Diabetes Mellitus* / metabolism
Diabetes, Gestational* / metabolism
Female
Fetus* / metabolism
Glucose / metabolism
Mice
Placenta / metabolism
Pregnancy

Substances

Glucose

Abstract

Publication types

MeSH terms

Substances

Grants and funding