AUTHOR=Zhu Hong , Luo Si-Si , Cheng Yi , Yan Yi-Shang , Zou Ke-Xin , Ding Guo-Lian , Jin Li , Huang He-Feng TITLE=Intrauterine Hyperglycemia Alters the Metabolomic Profile in Fetal Mouse Pancreas in a Gender-Specific Manner JOURNAL=Frontiers in Endocrinology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.710221 DOI=10.3389/fendo.2021.710221 ISSN=1664-2392 ABSTRACT=

Mounting evidence has shown that intrauterine hyperglycemia exposure during critical stages of development may be contributing to the increasing prevalence of diabetes. However, little is known about the mechanisms responsible for offspring metabolic disorder. In this present study, we explored intrauterine hyperglycemia exposure on fetal pancreatic metabolome, and its potential link to impaired glucose tolerance in adult offspring. Here, using a GDM mouse model, we found the metabolome profiling of pancreas from male and female fetus showing altered metabolites in several important pathways, including 5-methylcytosine, α-KG, branched-chain amino acids, and cystine, which are associated with epigenetic modification, insulin secretion, and intracellular redox status, respectively. This finding suggests that intrauterine exposure to hyperglycemia could cause altered metabolome in pancreas, which might be a metabolism-mediated mechanism for GDM-induced intergenerational diabetes predisposition.