Mechanism found: Why neurodevelopmental disorders affect more males than females

The study of mice, published in Nature Communications, led to the discovery that the O-linked N-acetylglucosamine transferase (OGT) molecule sets sex-specific patterns of gene expression.

Fresh research findings on the role of biological sex in disease risk

The study of mice, published in Nature Communications, led to the discovery that the O-linked N-acetylglucosamine transferase (OGT) molecule sets sex-specific patterns of gene expression.

A team from the University of Maryland School of Medicine looked into the OGT molecule, which plays an important role in placental health. The research suggests that the molecule uses an epigenetic modification, H3K27me3, that controls transcription which in itself provides scientists with hints to the molecular dynamics leading to the sex-specific disorder disparity. Epigenetics studies the changes of gene expression. 

One of the scientists in the research team, Dr. Tracy Bale, indicated that high levels of H3K27me3 in the female placenta can produce resilience to the stress experienced by the gestating mother. This would highlight one molecular pathway that may lead females to be more resilient to maternal stress than males. Dr. Bale has indicated that the such a pathway may be an explaining factor on the human neurodevelopmental difference. The presence of OGT and H3K27me3 in the placenta, Dr. Bale has explained,  is crucial to many protein encodings taking place during pregnancy, with the consequent implications and effects. The OGT gene is located in the X chromosome and may be providing a degree of fetal protection to females from the maternal environment. 

Sex has been determined to have a role in neurological and psychiatric conditions and also hypertension, diabetes or arthritis- In the cases of depression and anxiety, more females are affected while neurodevelopmental disorders ranging from the autism spectrum disorders, early-onset schizophrenia, and attention deficit hyperactivity, are more prevalent in males. Similarly, gestational stress, maternal infection, drug exposure and other forms of prenatal insults affect males more.

Prior to this mice study, Dr. Bale’s previous research has also determined that male parental stress in mice can affect the brain development of offspring. Stress, the findings indicates, has the capacity to alter a father’s sperm, in itself impacting a child’s brain development. Further mice work by Dr. Bale has found that chronic mild stress in male mice can lead to offspring with reduced hormonal response to stress, and therefore indicate a link to neuropsychiatric affections such as PTSD.

Bridget M. Nugent, Carly M. O’Donnell, C. Neill Epperson, Tracy L. Bale. Placental H3K27me3 establishes female resilience to prenatal insults. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-04992-1

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