Abstract
Gestational diabetes mellitus (GDM) is the most common pregnancy complication worldwide and may result in short-term and long-term consequences for offspring. The present review highlights evidence of epigenetic programming, mostly from human studies, which occurs in offspring exposed to maternal GDM during different stages of development, paying special attention to the differences in sensitivity of offspring to maternal hyperglycemia as a result of sex-related factors. We also aim to answer the following question: If these epigenetic changes are constant throughout the lifetime of the offspring, how do they present phenotypically?
Highlights
The first 1000 days, which starts from pre-conception until approximately two years of age, is the period during which tissues and organs are sensitive to several environmental factors which can shape their development and maturation and may program their susceptibility to diseases later in life
According to a very recent review by Nijs et al, among 23 studies published between the years 2000 and 2019, which aimed at evaluating the long-term metabolic risk in offspring from mothers suffering from Gestational diabetes mellitus (GDM), only seven evaluated possible sex differences [17]
Studies on human fetal endothelial cells from the umbilical cord vein, isolated from GDM pregnancies and healthy pregnancies exposed to high d-glucose concentrations for 48 h, demonstrated an increase in miR-101 expression and a decrease in expression of the enhancer of zester homolog 2 (EZH2), which is involved in the complex initiation and maintenance of the methylation of histone H3 on lysine 27, which in turn results in miR-101 downregulation
Summary
The first 1000 days, which starts from pre-conception until approximately two years of age, is the period during which tissues and organs are sensitive to several environmental factors which can shape their development and maturation and may program their susceptibility to diseases later in life. The increasing number of mothers depending on the heterogeneity of screening approaches, diagnostic criteria and population affected by GDM is probably related to advanced maternal age, which, in turn, is associated with characteristics, and its prevalence has increased constantly over the past few decades [3]. The short-term consequences of GDM include large-for-gestational-age infants, increased effects of GDM in offspring include a higher risk of developing obesity, metabolic syndrome, diabetes prenatal and perinatal mortality, prematurity, higher risk of cesarean section and increased perinatal mellitus type 2 (DM2) and cardiovascular disease later in life [7]. According to a very recent review by Nijs et al, among 23 studies published between the years 2000 and 2019, which aimed at evaluating the long-term metabolic risk in offspring from mothers suffering from GDM, only seven evaluated possible sex differences [17]. Data from the OBEGEST cohort study show that GDM is a risk factor for childhood overweight in boys but not in girls [23]
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