Prenatal Sex Hormone Exposure Is Associated with the Development of Autism Spectrum Disorder

Abstract

Sexual differentiation is a major developmental process. Sex differences resulting from sexual differentiation have attracted the attention of researchers. Unraveling what contributes to and underlies sex differences will provide valuable insights into the development of neurodevelopmental disorders that exhibit sex biases. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects an individual’s social interaction and communication abilities, and its male preponderance has been consistently reported in clinical studies. The etiology of male preponderance remains unclear, but progress has been made in studying prenatal sex hormone exposure. The present review examined studies that focused on the association between prenatal testosterone exposure and ASD development, as well as sex-specific behaviors in individuals with ASD. This review also included studies on maternal immune activation-induced developmental abnormalities that also showed striking sex differences in offspring and discussed its possible interacting roles in ASD so as to present a potential approach for future studies on sex biases in ASD.

Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder

“…In this review, we discussed neuroinflammation and oxidative stress as risk factors in the pathogenesis of ASD. The prenatal environment is not only a sensitive period for fetal development but also a vulnerable period for the onset of disorders such as NDDs and psychiatric disorders [ 9 , 10 , 11 , 192 ]. MIA, one of the environmental factors involved in the onset of ASD, induces neuroinflammation and oxidative stress in the offspring and directly or indirectly damages the placenta and fetal brain during embryonic stages ( Figure 1 ).…”

Excess neonatal testosterone causes male-specific social and fear memory deficits in wild-type mice

“…There are several circumstances in which a fetus may be exposed to excess testosterone, whether the source is the fetus, mother, or placenta (Baron-Cohen et al, 2015; Van De Beek et al, 2004). Congenital adrenal hyperplasia (CAH), Polycystic Ovarian Syndrome (PCOS), pre-eclampsia, and increased maternal psychological stress are conditions associated with increased androgen levels and have been associated with increased offspring risk for neurodevelopmental disorders (Davies, 2014; Gumusoglu et al, 2020; Knickmeyer and Baron-Cohen, 2006; Kumar et al, 2018; Lai et al, 2011; Li et al, 2023). Therefore, hormone dysregulation alone may be enough to induce related impairments in some, likely small, percentage of individuals.…”

Analysis of lncRNA, miRNA, mRNA-associated ceRNA networks in Autism

“…Many studies have shown that females with ASD show different characteristics than males with ASD. In addition, clinical studies have also reported that according to the different characteristics of ASD and camouflage, females with ASD are diagnosed much later than males with ASD [17]. Many genes are affected by risk mutations In ASD encoded proteins for synaptic, transcriptional and Chromatin remodeling pathways, which involve voltage ion channels regulating the release of action potentials, Acceleration and excitability-transcription coupling as well as histone modifying and chromatin remodeling enzymes [18].…”