Abstract

Autism and related neurodevelopmental conditions have high heritability and are often attributed to Genetics. Yet males are more likely to be diagnosed, even when the general spectrum of traits or alternative presentations are considered in females. Sex differences in the prenatal environment may then be interacting with genetic variance to ultimately affect neurodevelopment. Recent findings indicate that the placenta may be the key mediator of this interaction and an understudied source of neurodiversity in humans. This is supported by the following lines of evidence. First, steroid hormones such as estradiol are elevated in the fetal and maternal circulation of autistic males and correlate with the development of autistic traits. Second, subtle sex differences in placental function (e.g. in the levels of the placental growth factor) mediate sex differences in the future autistic traits of the offspring. Third, sex differences in placental gene expression are enriched for genes implicated in autism. Fourth, recent assessments of large population registries, such as the MBR in Sweden, show that males are more likely to have placental complications and complicated labour, compared to females, who, in turn, are more able to adjust their growth patterns prenatally. Finally, evolutionary adaptations in the primate lineage may show ‘changes of degree’ in humans, such as increased steroidogenesis, which may be linked to cortical expansion and for understanding the association between the placenta and conditions such as autism.