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母体1型糖尿病に曝露された乳児：子宮内エピジェネティック修飾と神経発達

Nieves Luisa González-González¹, Enrique González-Dávila², José Ramón Castro-Conde^1,3

¹Obstetrics and Gynecology Department, Facultad de Ciencias de la Salud, Sección de Medicina. University of La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.

Frontiers in endocrinology

|February 26, 2026

要旨

Background:

The relationship between the neurodevelopment in infants exposed to maternal Type-1 diabetes and changes in fetal DNA methylation has not yet been investigated.

Aim:

This hypothesis-generating study, we aimed to determine whether neurodevelopmental outcomes in offspring from mothers with Type-1 diabetes are associated with intrauterine epigenetic changes in fetal DNA.

Material And Methods:

We conducted a prospective, pilot case-control study, comparing infants exposed to maternal Type-1-diabetes with control infants. Cord blood DNA samples were analyzed using the TruSeq-Methyl-Capture-EPIC-Kit, covering over 3.3 million CpGs. The Bayley-III Scales were used to assess infant neurodevelopment, and the scores were correlated with the newborn DNA methylation data.

Results:

In infants exposed to maternal diabetes, we identified 108 differentially methylated genes enriched in pathways crucial for neurodevelopment: Vocal, Imitative and Observational Learning, Synapse Organization, and Neurogenesis. The greatest methylation differences were observed in differentially methylated regions (DMRs) annotated to key neurological genes: MYT1L (21.61%, q=1.97E-07), NRXN1 (12.30%, q=5.04E-75), SHANK3 (11.62%, q=9.81E-06) and KIRREL3 (7.35%, q= 1.53E-23). Both, NRXN1 and SHANK3, were enriched across all identified neurodevelopmental pathways. At two years of age, the infants exposed to maternal Type-1 diabetes scored significantly lower on the Bayley-III Scales across the cognitive, language, and motor domains. Methylation values across loci annotated to ten neurodevelopment-associated genes were linked to Bayley-III cognitive, language, and/or motor domain scores-with MYT1L and NRXN1 showing significant correlation with the Bayley-III language domain score.

Conclusions:

While further confirmation is needed, we provide the first results supporting the hypothesis that neurodevelopmental alterations observed in offspring of mothers with Type-1 diabetes are potentially associated with DNA methylation changes during intrauterine life which can be identified at birth.

キーワード:

DNA 臍帯血エピジェネティック遺伝子母体糖尿病メチル化神経発達 1型糖尿病

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