Dataset Information

Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring.

ABSTRACT: The etiology of Autism Spectrum Disorders (ASD) includes a strong genetic component and a complicated environmental component. Recent evidence indicates that maternal diabetes, including gestational diabetes, is associated with an increased prevalence of ASD. While previous studies have looked into possible roles for maternal diabetes in neurodevelopment, there are few studies into how gestational diabetes, with no previous diabetic or metabolic phenotype, may affect neurodevelopment. In this study, we have specifically induced gestational diabetes in mice, followed by behavioral and molecular phenotyping of the mice offspring. Pregnant mice were injected with STZ a day after initiation of pregnancy. Glucose levels increased to diabetic levels between E7 and E14 in pregnancy in a subset of the pregnant animals. Male offspring of Gestational Diabetic mothers displayed increased repetitive behaviors with no dysregulation in the three-chambered social interaction test. RNA-seq analysis revealed a dysregulation in genes related to forebrain development in the frontal cortex and a dysregulation of a network of neurodevelopment and immune related genes in the striatum. Together, these results give evidence that gestational diabetes can induce changes in adulthood behavior and gene transcription in the brain.

SUBMITTER: Aviel-Shekler K

PROVIDER: S-EPMC7688640 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring.

Aviel-Shekler Keren K Hamshawi Yara Y Sirhan Worood W Getselter Dmitriy D Srikanth Kolluru D KD Malka Assaf A Piran Ron R Elliott Evan E

Translational psychiatry 20201125 1

The etiology of Autism Spectrum Disorders (ASD) includes a strong genetic component and a complicated environmental component. Recent evidence indicates that maternal diabetes, including gestational diabetes, is associated with an increased prevalence of ASD. While previous studies have looked into possible roles for maternal diabetes in neurodevelopment, there are few studies into how gestational diabetes, with no previous diabetic or metabolic phenotype, may affect neurodevelopment. In this st ...[more]

PMID: 33239620

Similar Datasets

Project description:BackgroundWomen with hypertensive disorders in pregnancy are at an increased risk of cardiovascular disease and type 2 diabetes later in life. Offspring born from these hypertensive pregnancies have increased levels of cardiovascular risk factors; whether they are at an increased risk of type 2 diabetes is not known.ObjectiveThe objective of the investigation was to study the risk of type 2 diabetes in the adult offspring exposed to maternal preeclampsia or gestational hypertension in utero.Study designWe studied 5335 members of the Helsinki Birth Cohort Study, who were born between 1934 and 1944 and who lived in Finland in 1995 when the National Medication Purchase Register was initiated. We ascertained gestational hypertension and preeclampsia according to modern criteria by using maternal and birth records. We defined type 2 diabetes through purchases of antidiabetic medication recorded in the comprehensive National Medication Purchase Register, excluding the 31 subjects who had purchased only insulin. We used Cox regression to assess hazard ratios for type 2 diabetes.ResultsA total of 590 men (21.6%) and 433 women (16.9%) had purchased medication for diabetes. The hazard ratio for type 2 diabetes for offspring exposed to any maternal hypertension in pregnancy was 1.13 (95% confidence interval, 1.00-1.29; n = 1780). For maternal gestational hypertension, it was 1.15 (95% confidence interval, 1.00-1.33; n = 1336) and for preeclampsia 0.98 (95% confidence interval, 0.71-1.34; n = 231). For type 2 diabetes with first medication purchase before 62 years, the corresponding hazard ratios were 1.25 (95% confidence interval, 1.04-1.51); 1.28 (95% confidence interval, 1.05-1.58), and 1.18 (95% confidence interval, 0.75-1.84). The hazard ratios were similar when adjusted for birthweight SD score for gestation, length of gestation, maternal body mass index in late pregnancy, height, age, and parity and for childhood or adult socioeconomic position. An increased risk of type 2 diabetes was also associated with low birthweight SD score, independent of the association with gestational hypertension.ConclusionOffspring exposed to maternal gestational hypertension in utero have an increased risk of type 2 diabetes in late adult life. This finding underlines the role of the whole spectrum of hypertensive disorders of pregnancy as risk factors of offspring disease throughout life. It also reinforces previous suggestions that adult health care providers should incorporate birth histories when evaluating an individual's risk to develop type 2 diabetes.

Dataset Information

Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring.

Publications

Gestational diabetes induces behavioral and brain gene transcription dysregulation in adult offspring.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets