Stress has a funny way of sneaking up on you, and with the newly understood dangers of stress being transmitted across generations, keeping the drama to a minimum is huge concern for expecting mothers. So, wouldn’t it be nice to have some sort of an early stress warning device? Placental miRNAs have already been used to predict infant behavior and now a team from the University of Pennsylvania adds to the power of placenta by uncovering a single gene biomarker that can act as early indicator of maternal stress, which can increase the risk for neurodevelopmental disorders.
The U Penn team had previously found that O-GlcNAc transferase (OGT) could serve as a placental biomarker in their stressed out mom model. In this study, they used a nifty combo of genome editing and ChIP-seq techniques to create and investigate a transgenic mouse model with targeted placental disruption of Ogt (Pl-OGT). Here’s what they found:
- Their brand new hemizygous mice had similar gene expression profiles to their early stress placentas.
- OGT levels were lower in males compared to females and were further decreased following maternal stress.
- ChIP-Seq for the O-GlcNAc mark identified the 17 beta hydroxysteroid dehydrogenase-3 (Hsd17b3) locus in male EPS placentas, which correlated with a reduction in Hsd17b3 expression.
- The Pl- OGT adult offspring had reduced body weights and elevated hypo- thalamic–pituitary–adrenal stress axis responsivity, reminiscent of the phenotypes previously reported for the Early Prenatal Stress males.
- The phenotype was mostly found in males, leaving an intriguing gender bias.
Together, the work confirmed OGT as in important placental biomarker of maternal stress and demonstrated the profound impact a single placental gene has on long- term metabolic and neurodevelopmental programming that may be related to an increased risk for neurodevelopmental disorders. Senior author Tracy Bale shares that “OGT seems to be serving a role as the ‘canary in the coal mine,’ offering a readout of mom’s stress to change the baby’s developing brain.”
Learn all about molecular warning signs in PNAS, July 2014