The researchers' study of mice, published online in the journal Brain, Behavior and Immunity, found the hippocampus -- the part of the brain responsible for memory and spatial navigation -- was smaller over the long term in male offspring exposed to the overactive immune system in the womb.
The males also had fewer nerve cells in their brains, and their brains contained a type of immune cell that should not be present, the study found.
"Our research suggests that in mice, males might be more vulnerable to the effects of maternal inflammation than females, and the impact may be lifelong," Dr. Irina Burd of the Johns Hopkins University School of Medicine in Baltimore, the study leader and director of the Integrated Research Center for Fetal Medicine, said in a statement.
"Now we wonder if this could explain why more males have diseases such as autism and schizophrenia, which appear to have neurobiological causes."
For the study using mice, the researchers sought to mimic the effects of a maternal infection or other condition that causes inflammation in a pregnant mother. This type of inflammation, occurring between 18 and 32 weeks of gestation in humans, has been linked to preterm birth, and it may be responsible for an imbalance of immune cells in the brain of the offspring and even death of nerve cells in the brains of those children.
Burd and colleagues said one group of pregnant mice got saline injections into the womb, while another group got injections of lipopolysaccharide, a toxin meant to generate the kind of inflammatory effects of E. coli bacteria without the presence of the germ itself.
Soon after birth, the lipopolysaccharide group showed poor motor skills and behavioral issues such as hyperactivity. At 60 days post-weaning -- the equivalent of mouse adulthood -- the lipopolysaccharide mice could walk well but were still hyperactive, suggesting the motor problems were resolved -- possibly through some type of rewiring of the brain -- but the behavioral problems were not.
"All this time later, something was still going on in their brains," Burd said.
The sex-specific differences: the smaller hippocampus, the presence of fewer nerve cells, the existence of immune system macrophages -- remove dying or dead cells and cellular debris in places they shouldn't be -- were also found in adulthood, the study said.
Chronic inflammation, Burd said, might play a role in keeping the hippocampus small, potentially because it inhibits proper brain development. But why males and females respond differently to the same stressor in utero remains a question, Burd said.