Downregulation of peroxisome proliferator-activated receptor gamma in the placenta correlates to hyperglycemia in offspring at young adulthood after exposure to gestational diabetes mellitus

Abstract

Aims/Introduction: Children who are exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing related illnesses, such as type 2 diabetes mellitus in young adulthood, but the underlying mechanism and related predictive biomarkers are not known. Materials and Methods: The present study identified the related biomarkers of hyperglycemia in young adults from the relationship between fetal blood glucose and placental lipid transporters at messenger ribonucleic acid (mRNA) and protein expression levels. We recruited patients from a prospective cohort, and determined the mRNA and protein levels of placental fatty acid transporters. Diet-induced mouse models of GDM were established, and the mRNA and protein levels of the same transporters in placentas were validated. Results: Only the mRNA levels of peroxisome proliferator-activated receptor gamma correlated with the levels of neonatal blood glucose in GDM patients using linear regression and Spearman's correlation analyses (r = 0.774, P = 0.001). The mRNA levels of peroxisome proliferator-activated receptor gamma, matrix metalloproteinase-2 and fatty acid transport protein-6 correlated with blood glucose levels in mouse offspring (r = 0.82, P = 0.001, r = 0.737, P = 0.006 and r = −0.891, P = 0.001, respectively) at young adulthood using the same analyses. Notably, we observed significantly higher blood glucose levels in GDM offspring at 12 weeks-of-age compared with the control and rosiglitazone-supplemented groups (P < 0.05). Conclusions: The downregulation of peroxisome proliferator-activated receptor gamma in the placenta might predict hyperglycemia in offspring at young adulthood.