Developing Male Brain Exposed to Less Stress-Protective Protein

Mouse Findings Could Help Explain Sex Differences in Schizophrenia, Autism

March 12, 2013 • Science Update

Why are rates of schizophrenia and autism higher in males? New evidence implicates an enzyme expressed in the placenta that helps protect the developing fetal brain from adverse effects of maternal stress early in pregnancy. Video: NIMH grantee Tracy Bale, Ph.D., of the University of Pennsylvania, discussed her line of research into how maternal stress might differentially affect the developing male brain during an interview at the 2011 Society for Neuroscience meeting.

Since then, Bale and colleagues discovered in mice that the gene that makes the enzyme, called OGT, is expressed less in placentas of male than in female offspring. Moreover, OGT was also expressed at relatively lower levels in placentas from stressed mothers. When they looked at evidence of its expression in human placentas, they saw a similar pattern of sex differences. Further experiments in mice confirmed that OGT plays a pivotal role in regulating the turning on-and-off of hundreds of brain genes and in protecting the developing brain from insults. The researchers suggest that OGT epigenetically  places male fetuses at a disadvantage in adapting to environmental changes – a possible mechanism underlying males’ increased vulnerability to enduring effects of maternal stress on brain development.

Reference

Howerton CL, Morgan CP, Fischer DB, Bale TL. O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development. PNAS, March 5, 2013

Grant: 5 R01 MH091258 04