Atlas of Fetal Metabolism During Mid-to-late Gestation and Diabetic Pregnancy

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2023 Dec 9

PMID 38070508

Authors

Cesar A Perez-Ramirez

Haruko Nakano

Richard C Law

Nedas Matulionis

Jennifer Thompson

Andrew Pfeiffer

Junyoung O Park

Atsushi Nakano

Heather R Christofk

Affiliations

Soon will be listed here.

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 C-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 C-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.

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