Marques epigenètiques del desenvolupament prenatal

Abstract

Epigenetics has been involved in the relationship between maternal overnutrition and fetal development. The placenta is a transitory tissue that regulates the endocrinometabolic functions and development of the fetus. Imprinted genes have an important role in the function of the placenta and fetal growth, and are regulated through DNA methylation. Among the imprinted genes in placenta there are the gene clusters DLK1-DIO3 and C19MC. In this context, the objectives of the study were: (I) to study the DNA methylation of DLK1-DIO3 and C19MC in placenta; and (II) to study the association between the methylation of these genes and the anthropometric and endocrinometabolic parameters of pregnant women and their respective children. In order to achieve the objectives, a cohort of 60 pairs of pregnant woman-child from the region of Alt Empordà was studied with available clinical data. DNA was extracted from the placenta, bisulfited and the region of interest was amplified with specific primers for bisulfited DNA. The obtained product was pyrosequenced to quantify the percentage of methylation of each CpG. The results were statistically analyzed with SPSS software and significance level was set at p=0.05. No significant differences were found regarding the methylation profile of the studied regions of DLK1-DIO3 and C19MC when comparing the 4 study groups (control (1) group compared with (2) pregestational with gestational obesity, (3) pregestational obesity and (4) gestational obesity). However, the percentage of methylation of DLK1-DIO3 positively correlated with maternal blood pressure and glycated hemoglobin (HbA1C), whereas the methylation in C19MC was associated with maternal insulin, triglycerides and total cholesterol. Regarding their respective children, no significant relationships were found. After correcting for multiple testing, total maternal cholesterol was still associated with the methylation level of C19MC (r=0.624; p=0.004). In a multivariate linear regression test, maternal total cholesterol correlated independently with the C19MC methylation percentage, explaining a 43% of the variance (β=0.682; p=0.001). In conclusion, maternal total cholesterol and the methylation level of C19MC in placenta are related, and as a consequence they could affect fetal endocrinometabolic development