Epigenetic Alterations Related to Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is the most common metabolic complication in pregnancy, which affects the future health of both the mother and the newborn. Its pathophysiology involves nutritional, hormonal, immunological, genetic and epigenetic factors. Among the latter, it has been observed that alterations in DNA (deoxyribonucleic acid) methylation patterns and in the levels of certain micro RNAs, whether in placenta or adipose tissue, are related to well-known characteristics of the disease, such as hyperglycemia, insulin resistance, inflammation and excessive placental growth. Furthermore, epigenetic alterations of gestational diabetes mellitus are observable in maternal blood, although their pathophysiological roles are completely unknown. Despite this, it has not been possible to determine the causes of the epigenetic characteristics of GDM, highlighting the need for integral and longitudinal studies. Based on this, this article summarizes the most relevant and recent studies on epigenetic alterations in placenta, adipose tissue and maternal blood associated with GDM in order to provide the reader with a general overview of the subject and indicate future research topics.

Keywords: DNA methylation; adipose tissue; epigenetics; gestational diabetes; miRNAs; placenta.

Figure 1

The main placental epigenetic alterations associated with GDM. Epigenetic alterations and their effects on target genes are shown (see the text for deeper details). Interestingly, some explain, in part, the well-known pro-inflammatory status and excessive growth of the placenta. On tissue, solid arrows indicate up-regulation or down-regulation in maternal circulation and the fetus indicate low or high circulating levels. Dotted line arrows indicate association. HDL-cholesterol: high-density lipoprotein cholesterol; mRNA: messenger ribonucleic acid; FFA: free fatty acids; PPARα: proliferator-activated receptor alpha; NF-κB: nuclear factor-kappa B; TNF-α: tumoral necrosis factor alpha; IL-1β: interleukin 1 beta; IL-6: interleukin 6; COX-2: cytochrome C oxidase subunit II; HIF3A: hypoxia inducible factors 3A; MECP2: methyl CpG binding protein 2; DNMT1, DNA methyltransferase 1; TBL1X: transducin β–like protein 1; LEP: leptin.

Figure 2

The main epigenetic alterations in visceral adipose tissue associated with GDM. Epigenetic alterations and their effects on target genes are shown (see the text for deeper details). These findings explain in part the well-known pro-inflammatory status, decreased production of adiponectin and insulin resistance in visceral adipose tissue. In tissue, solid line arrows indicate or up-regulation or down-regulation; in maternal circulation they indicate low or high circulating levels. Dotted arrows indicate associations. TNF-α: tumoral necrosis factor alpha; ADIPOQ: adiponectin; ERα: estrogen receptor alpha; GLUT4: glucose transporter 4.