Sex Bias in Maternal Immune Activation-Induced Neurodevelopmental Disorder Begins at the Placenta

• DOI: 10.2139/ssrn.3640834
• Publication Date: 2020-07-28T11:31:59Z
• Authors: Elizabeth L. Frost; David M. Johanson; Catherine R. Lammert; Calli E. Bellinger; Mariah E. Hurt; Morgan K. Wall; Ashley C. Bolte; Hannah E. Ennerfelt; Eli R. Zunder; John Lukens
• Keywords: Neurodevelopmental disorder

Systemic maternal inflammation during pregnancy is increasingly thought to be a risk factor for development of autism spectrum disorder (ASD), which diagnosed at rate 4-fold higher in males than females. Administration the viral mimic polyI:C pregnant mice mid-gestation leads ASD-related phenotypes offspring, consisting deficits communication and socialization, as well repetitive behaviors. In this model immune activation (MIA), elevated production serum cytokines known promote alterations fetal neurodevelopment. Although male female littermates are exposed same inflammation, we show that behavioral can elicited preferentially mirroring sex bias observed human ASD. Because placenta partially derived from cells first site exposure hematogenous hypothesized sex-specific reactions MIA may originate characterization these differences offer new insights into orgins neurodevelopmental disorders. To characterize responses maternal-fetal interface, conducted bulk RNA sequencing polyI:C- saline-treated embryos several time points post-injection. We identified male-biased elevation expression inflammatory signatures involving neutrophils, innate signaling, antigen presentation. Placental transcriptomics analysis also male-specific downregulation cholesterol fatty acid synthesis gene signature suggesting failing placental health. Interestingly, found induced differential large percentage high-risk genes placenta. These findings shed light on how interface shape help reveal molecular players underpinning