Why Are Males At More Risk For Developing Neurodevelopmental Disorders?

Scientists have recently discovered why males are more at risk for developing neurodevelopmental disorders and how biological sex affects one’s chance of disease.

Dr. Tracy Bale, a professor of pharmacology from the University of Maryland School of Medicine along with her colleagues, conducted a study on mice to understand the truth behind this gender disparity.

The research focused on a specific molecule that is vital in placental health.

They discovered that a molecule known as O-linked N-acetylglucosamine transferase (OGT) functions by forming sex-specific patterns of gene expression.

The molecule appears to work through an epigenetic modification that mainly directs transcription, H3K27me3.

Epigenetics is the study of changes in organisms that are caused by the alteration of gene expression rather than modification of the genetic code itself.

High levels of H3K27me3 in the female placenta generates resilience to stress experienced by the mother.

This shows a molecular pathway that enables females to be more resilient to maternal stress compared to males.

“This pathway could help explain why we see this profound neurodevelopmental difference in humans,” said Dr. Bale.

“OGT and H3K27me3 in the placenta are crucial to a lot of protein encoding that occurs during pregnancy, and so this process has a lot of downstream effects. The OGT gene is on the X chromosome, and seems to provide a level of protection for the female fetus to perturbations in the maternal environment,” she added.

Scientists are now beginning to realize that sex plays a significant role when it comes to the risk of disease.

Males are more at risk of developing neurodevelopmental disorders, such as ADHD and autism spectrum disorders, while females are more prone to mental illness, including anxiety and depression.

The association between stress and the succeeding risk for the development of neurodevelopmental disorders, such as schizophrenia and autism in children, has been the focus of Dr. Bale’s research.

Results of the study was recently published in the Nature Communications journal.

Link:  https://medicalxpress.com/journals/nature-communications/

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