Pregnancy Protein Implicated in Neurodevelopmental Disorders

Researchers investigating the causes of autism and schizophrenia have discovered a protein that may play a role in these neurodevelopmental disorders. The level of the protein is affected by serious physical or emotional stress women experience during their pregnancy.

Expectant mothers who are stressed during pregnancy transmit lower levels of a unique protein to their developing fetuses through the placenta, according to a new study by researchers at the University of Pennsylvania in Philadelphia. The lowest level is found in the placentas of male offspring.

Tracy Bale, a professor of neurology at the school and senior author of the study, said the placenta, which transfers blood, oxygen and nutrients to the unborn child, also acts as a filter that responds to a pregnant woman’s changing environment.

“So, it has genes that are expressed that produce these functions. But those genes can change in response to mom’s stress, mom’s dietary changes, mom’s immune responses, etc.,” said Bale.

Schizophrenia is marked by hallucinations and difficulty connecting with the outside world. Autistic individuals have impaired communication and social interaction skills.

Knowing that the conditions tend to affect males more often and more severely than females, Bale and colleagues set about looking for a biomarker, a protein that might provide clues for the gender difference.

Investigators reasoned that a gene that plays a role in the neurodevelopmental conditions might be linked to the female X-chromosome.

In experiments with mice, investigators stressed the rodents during their first week of pregnancy, which is equivalent to the first three months of a human pregnancy, with the odor of a predator and unfamiliar noises. They then performed a detailed genetic analysis of the animals’ placentas, and those of unstressed mice. 

Researchers discovered a protein, called OGT, that seems to be present in higher levels in the female placentas than in the placentas of male offspring. The OGT levels also were lower in the placentas of the stressed mice overall compared to the unstressed rodents.

Investigators also manipulated levels of the protein in a mouse model, discovering that rodents with half the normal amount of OGT had changes in hundreds of different genes known to be involved in neurological development. In addition, researchers examined discarded human placentas and found lower levels of the protein in male placental tissue.

Bale cannot say with certainty whether OGT affects neurodevelopment in humans. But she said the biomarker could lead to a test to identify babies at increased risk for autism and schizophrenia due to pregnancy stress.

“You would know which babies to follow to keep an eye on them, to determine if they are at a greater risk. And they may be presenting earlier with different stress reactivity levels, behavioral changes that would predispose them,” said Bale.

In the case of autism, research suggests that early intervention is helpful in improving communication skills.