title: A sexually dichotomous, autistic-like phenotype is induced by Group B Streptococcus maternofetal immune activation.
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.
authors.affiliation: Department of Pediatrics, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Marie-Julie
authors.initials: MJ
authors.lastname: Allard
authors.affiliation: Département de Pédiatrie, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Julie D
authors.initials: JD
authors.lastname: Bergeron
authors.affiliation: Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Moogeh
authors.initials: M
authors.lastname: Baharnoori
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Lalit K
authors.initials: LK
authors.lastname: Srivastava
authors.affiliation: Département de Microbiologie et d'Infectiologie, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Louis-Charles
authors.initials: LC
authors.lastname: Fortier
authors.affiliation: INSERM U 1016, Institut Cochin, Team Barriers and Pathogens; DHU Risques et grossesse, Hôpitaux Universitaire Paris Centre, Université Paris Descartes, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Poyart
authors.affiliation: Department of Pediatrics, Research Institute of the McGill University Health Centre, McGill University, Montreal, Quebec, Canada.|Département de Pédiatrie, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sébire
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000382:microbiology*; D001522:Behavior, Animal; D002821:Chorioamnionitis / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D010641:Phenotype; D011247:Pregnancy; D051381:Rats; D011917:Rats, Inbred Lew; D013290:Streptococcal Infections / Q000150:complications*; D013291:Streptococcus / Q000276:immunology*
keywords: Group B Streptococcus; autism spectrum disorders; behavior; chorioamnionitis; inflammation; prenatal infection