Fetal gastroschisis: Maternal and fetal methylation profile

Abstract

Objective: The purpose of this study was to describe the genomic deoxyribonucleic acid (DNA) methylation profile in fetuses with gastroschisis, determine whether the profile was inherited, and investigate any possible correlations with maternal risk factors. Method: Genome-wide DNA methylation analysis of 96 blood samples was performed using the Illumina Human Methylation 850K BeadChip. The blood samples were collected as follows: 32 from the umbilical cord of fetuses with gastroschisis, 32 from their respective mothers, 16 from the umbilical cord of fetuses without malformation, and 16 from their respective mothers. Results: The differential DNA methylation analysis showed a significant difference between the groups. The enrichment analysis resulted in 12 sites related to T-cell activation (p ¼ 0.0128). The sites with different methylation status contained 10 genes, three of which were related to the beta-2-microglobulin gene. The methylation profile observed in the fetuses with gastroschisis was not inherited from the mothers. In addition, there was no association between maternal urinary tract infection, smoking, and alcohol use and different methylated sites. Conclusion: We established the methylation profile of gastroschisis fetuses, which differs from that of normal fetuses. The profile was not inherited and did not correlate with maternal risk factors. Key Points What is known about this topic? � The etiology and pathogenesis of fetal gastroschisis and its association with environmental factors are not clearly understood, and attempts to identify a biological marker have not been successful. No previous investigation into the methylation patterns in pregnant women carrying fetuses with gastroschisis has been published What does this study add? � This study provides the methylation pattern of fetuses with gastroschisis

The complex search for the cause of gastroschisis

“…We found that the two gastroschisis cases of this study had a hypomethylation status in relation to the control group. This differed from the finding of our previous study, which detected a hypermethylated status in the gastroschisis group (with a greater transcriptional block) (Freitas et al, 2021). The two cases were analyzed separately from the previously published cases because of their particular histories, namely a recurrence in the consanguineous couple and a mother's gastroplasty.…”

“…Furthermore, we expected to find a hypermethylated profile, that is, a profile blocked for a biological process possibly associated with a failure to close the abdominal wall in fetuses with gastroschisis. We also expected to find an alteration for T-cell activation, as observed in the previous study (Freitas et al, 2021). Instead, we found a predominantly hypomethylated profile in both Case 1 and Case 2, none of them associated with T-cell activation.…”

“…The umbilical cord sample was collected at delivery soon after cord clamping. The control group comprised 16 low‐risk pregnant women with their respective fetuses without malformation (Freitas et al, 2021). At study entry the characteristics of the control group were mean maternal age of 20.94 ± 3.59 years, BMI of 23.32 ± 3.40, and gestational age of 24.14 ± 4.94 weeks.…”

“…The methylation profile was investigated as previously described (Freitas et al, 2021); the methylation array was performed for all samples (five study samples and 32 control samples), and the single nucleotide polymorphism (SNP) array was performed only for the two fetuses with gastroschisis. Major details about the study protocol were reported previously 1 (Centofanti et al, 2018; Centofanti et al, 2019; Freitas et al, 2021). The genomic positions were reported according to the Homo sapiens reference genome (hg19, Genome Reference Consortium GRCh37 build, Feb/2009).…”

“…More recent methodologies for genetic variations and gene expression analysis, such as array‐MLPA (multiplex ligation‐dependent probe amplification) and new generation sequencing, have been used to identify genetic changes and biological pathways that converge to form the clinical picture of diseases. We have recently investigated the methylation profile in gastroschisis fetuses to search for the genomic regions possibly involved in the disease's etiology and to analyze the environmental factors to which the pregnant women were exposed (Freitas et al, 2021). In this study, fetuses with gastroschisis showed a noninherited hypermethylated profile mainly related to T‐cell activation.…”