A sexually dichotomous, autistic-like phenotype is induced by Group B Streptococcus maternofetal immune activation
Marie-Julie Allard1, Julie D Bergeron2, Moogeh Baharnoori3
1Department of Pediatrics, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
Insights
Maternal Group B Streptococcus (GBS) infection during pregnancy can harm uninfected offspring. Gestational GBS exposure in rats led to neurodevelopmental issues and autistic-like behaviors in male pups.
Area of Science:
- Neuroscience
- Developmental Biology
- Microbiology
Background:
- Group B Streptococcus (GBS) commonly colonizes pregnant women but its impact on offspring neurodevelopment is unknown.
- GBS causes chorioamnionitis and newborn cerebral injuries, often without direct pathogen transfer.
- No preclinical studies examined maternal GBS exposure's effect on offspring brain development and behavior.
Purpose of the Study:
- To investigate the neurodevelopmental impact of maternal GBS infection on uninfected offspring.
- To establish a preclinical rat model for studying GBS-induced gestational effects.
- To analyze placental and neurodevelopmental outcomes in offspring exposed to GBS in utero.
Main Methods:
- A preclinical rat model was used to expose pregnant dams to GBS.
- Placental tissues were examined for signs of chorioamnionitis.
- Neurodevelopmental features and behaviors of male and female offspring were assessed.
Main Results:
- GBS exposure caused chorioamnionitis in placentas, with more inflammation in males.
- Male offspring exhibited reduced periventricular white matter thickness.
- GBS-exposed male offspring displayed autistic-like behaviors, including social deficits and hyperactivity.
Conclusions:
- Gestational GBS exposure can cause neurodevelopmental abnormalities in offspring.
- These findings suggest GBS infection is a potential environmental factor in autism spectrum disorders (ASD) pathophysiology.
- This study highlights a common, modifiable infectious agent's role in ASD.
Abstract:
Group B Streptococcus (GBS) is a commensal bacterium present in the lower genital tract of 15-30% of healthy pregnant women. GBS is the leading cause of chorioamnionitis and cerebral injuries in newborns, occurring most often in the absence of maternofetal pathogen translocation. Despite GBS being the most frequent bacterium colonizing pregnant women, no preclinical studies have investigated the impact of end-gestational maternal GBS exposure on the offspring's brain development and its behavioral correlates. Our hypothesis is that GBS-induced gestational infection/inflammation has a deleterious neurodevelopmental impact on uninfected offspring. Our goal was to study the impact of maternal GBS infection on the placental and neurodevelopmental features in the offspring using a new preclinical rat model. GBS-exposed placentas exhibited chorioamnionitis characterized by the presence of Gram-positive cocci and polymorphonuclear cells, with the latter being significantly more prominent in the labyrinth of male offspring. GBS-exposed male offspring had reduced thickness of periventricular white matter. In addition, they exhibited autistic-like behaviors, such as abnormal social interaction and communication, impaired processing of sensory information and hyperactivity. Overall, these data show for the first time that gestational exposure to GBS plays an important role in the generation of neurodevelopmental abnormalities reminiscent of human autism spectrum disorders (ASD). These results provide new evidence in favor of the role of a common and modifiable infectious/inflammatory environmental factor in human ASD pathophysiology. Autism Res 2017, 10: 233-245. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
