Abstract
AimsGestational diabetes mellitus (GDM) can lead to short- and long-term complications for the child. Epigenetic alterations could contribute to explaining the metabolic disturbances associated with foetal programming. Although the role of the FTO gene remains unclear, it affects metabolic phenotypes probably mediated by epigenetic mechanisms. The aim of this study was to assess whether placental DNA epigenetic modifications at FTO promoter-associated cysteine–phosphate–guanine (CpG) sites are correlated with GDM. A secondary aim was to evaluate the association between the placental FTO DNA methylation and the maternal metabolic traits in women with and without GDM.MethodsSocio-demographic characteristics, clinical parameters at the third trimester of pregnancy, Mediterranean diet adherence, and physical activity were assessed in 33 GDM women and 27 controls. Clinical information about the newborns was registered at birth. The FTO rs9939609 (T > A) was genotyped.ResultsNo association between FTO DNA methylation and GDM was found. DNA methylation on the maternal side at the CpG1 was associated with maternal smoking in GDM (p = 0.034), and DNA methylation at the CpG3 was correlated with smoking or former smoking in controls (p = 0.023). A higher level of TGs was correlated with higher foetal placental DNA methylation at the CpG2 (p = 0.036) in GDM. An inverse association between HDL-C and maternal placental DNA methylation at the CpG3 in controls (p = 0.045) was found. An association between FTO rs9939609 and neonatal birthweight (p = 0.033) was detected.ConclusionsIn the awareness that the obesity pathophysiology is complex, the study adds a piece to this intricate mosaic.
Highlights
This article belongs to the topical collection Pregnancy and Diabetes, managed by Antonio Secchi and Marina Scavini.Gestational diabetes mellitus (GDM) is the most common metabolic disorder, and it is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes1 3 Vol.:(0123456789)Acta Diabetologica (2021) 58:997–1007 prior gestation [1]
The present study aimed to evaluate the relationship between the exposure to an altered intrauterine environment and foetal metabolic programming, focusing on GDM and DNA methylation profiles at promoter-associated CpG islands of the fat mass and obesity-associated (FTO) gene
Our study focused on methylation profiles of the FTO gene on both the maternal and foetal sides of the placenta in pregnant women with and without GDM
Summary
This article belongs to the topical collection Pregnancy and Diabetes, managed by Antonio Secchi and Marina Scavini.GDM is the most common metabolic disorder, and it is defined as diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes1 3 Vol.:(0123456789)Acta Diabetologica (2021) 58:997–1007 prior gestation [1]. Some maternal metabolic factors, including pre-pregnancy overweight/obesity and GDM, influence the foetal growth trajectories and affect children’s susceptibility to lifetime chronic diseases, including possible transgenerational effects [12, 13]. This mechanism fits well with the Developmental Origins of Health and Disease (DOHaD) hypothesis, which proposes that the origin of chronic diseases is related to a prenatal exposure to a suboptimal foetal environment [14, 15]. In its role as a controller of maternal foetal nutrient exchanges via epigenetic mechanisms, placenta responds to foetal demands and maternal availability of nutrients [16]
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