General anesthesia, germ cells and the missing heritability of autism: an urgent need for research

Abstract

Agents of general anesthesia (GA) are commonly employed in surgical, dental and diagnostic procedures to effectuate global suppression of the nervous system, but in addition to somatic targets, the subject's germ cells-from the embryonic primordial stage to the mature gametes-may likewise be exposed. Although GA is generally considered safe for most patients, evidence has accumulated that various compounds, in particular the synthetic volatile anesthetic gases (SVAGs) such as sevoflurane, can exert neurotoxic, genotoxic and epigenotoxic effects, with adverse consequences for cellular and genomic function in both somatic and germline cells. The purpose of this paper is to review the evidence demonstrating that GA, and in particular, SVAGs, may in some circumstances adversely impact the molecular program of germ cells, resulting in brain and behavioral pathology in the progeny born of the exposed cells. Further, we exhort the medical and scientific communities to undertake comprehensive experimental and epidemiological research programs to address this critical gap in risk assessment.

Keywords: DNA damage; autism spectrum disorder; gene expression; general anesthesia; germ cells; halogenated anesthetic gases; intergenerational epigenetic inheritance; sevoflurane; transcriptional dysregulation.