Contribution of maternal hypertension to autism etiology in a murine model; cerebellar gene expression

Abstract

Aim: To study the contribution of maternal hypertension to autism spectrum disorders’ (ASD) phenotype, and gene expression, in a murine model. Materials & methods: To examine the effects of maternal hypertension, we used a well-described transgenic mouse model lacking functional endothelial nitric oxide synthase (eNOS or NOS3). Behavioral testing was performed on male offspring between 8 and 10 weeks of age. Cerebella underwent shotgun transcriptome RNA sequencing. Differentially expressed genes were examined for Gene Ontology enrichment. 2-way-RM-ANOVA, 1-way-ANOVA and Student's t-test were used for statistical analysis. Results & conclusion: Our findings revealed that a deficit in social behavior, the hallmark of ASD, is differentially present in offspring born to hypertensive mothers. Novel ASD-related genes were differentially expressed in the cerebellum, implicating its possible role in ASD etiology. Condensation: Altered uterine environment resulting from maternal hypertension contributes to ASD phenotype, and modifies expression of novel ASD-related genes in cerebella of eNOS heterozygous offspring.

KEYWORDS:

• autism spectrum disorders
• behavior
• cerebellum
• eNOS
• genes
• maternal hypertension
• offspring

Disclaimer

This work was previously presented at the 35th Annual Meeting of the Society of Maternal Fetal Medicine in San Diego, CA, USA, 2–7 February 2015.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors thank AN Moore and A Srikrishnan for the critical reading of the manuscript.