This Enzyme Brings Us Closer to Understanding Sex-Biased DiseasesWe are beginning to unveil the molecular processes that makes females different from males. Last month, scientists located a DNA switch on the Y chromosome that turns female embryos into males. Now, a study has been published in Nature Communications which highlights the key role played by enzyme O-linked N-acetylglucosamine transferase (OGT) in placental health. 

The OGT molecule is expressed via the X-linked gene Ogt and is thought to act as a epigenetic modifier, more specifically for H3K2me27 mark. Epigenetics is the study of changes in how genes are expressed. The epigenetic marks differ from male to females. 

Dr. Tracy Bale, researcher at the University of Maryland, showed that high levels of H3K27me3 in the female placenta produce resilience to stress experienced by the mother. This indicates at least one molecular pathway that allows females to be more resilient to maternal stress than males.

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“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.”

Although additional studies are needed to further define how placental OGT impacts the epigenomic landscape responsible for healthy in utero development, the findings provide evidence that its regulation of H3K27me3 is critical in determination of trans-placental signals involved in brain programming. These outcomes validate the importance of the placenta as an active intercessor between the maternal milieu and fetal development, and demonstrate that sex differences in placental genetic and epigenetic patterning are critical in this process.

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