The Relationship of Steroid Hormones, Genes Related to Testosterone Metabolism and Behavior in Boys With Autism in Slovakia

Abstract

sis of autism and fetal testosterone levels were positively correlated with autistic traits in general population. [1][2][3][4] In addition, females with conditions of abnormal prenatal exposure to testosterone and its sex steroid precursors, such as congenital adrenal hyperplasia and polycystic ovary syndrome, were found to have higher rate of autistic traits as well as their children were of higher risk of developing autism. 5,6 However, the exact mechanism by which these hormones influence the manifestation of autistic traits remains undiscovered. Another model explaining higher prevalence of ASD in males is a female protective model which suggests that multiple genetic factors contribute to the development of ASD and that higher threshold of genetic liability is required in females compared to males. 7 Zhang et al. 8 demonstrated genetic evidence of sex differences in ASD confirming female protective model, employing investigation of de novo mutations, common variants of ASD candidate genes and their co-expression in male and female brains. Genetic architecture of ASD involves rare and de novo variants that were identified in studies using whole genome or exome sequencing technologies as well as low-risk com-

Sex and age differences in social and cognitive function in offspring exposed to late gestational hypoxia

“…ASD has been associated with altered circulating steroid hormones levels (e.g., testosterone, cortisol, estradiol) [27,[44][45][46][47][48][49][50][51][52]. We did not observe any effects on circulating testosterone levels or testosteroneassociated behaviors (e.g., aggression) in offspring exposed to gestational CIH.…”

“…Differences in steroid hormones, (e.g., testosterone, cortisol, estrogen) during gestation and later in life may also contribute to the phenotype of ASD [44][45][46][47][48]. The intensity of social impairments, repetitive behaviors, and precocious puberty in ASD has been correlated to testosterone and estradiol levels [27,49,50]. Further, elevated diurnal cortisol may contribute to comorbid anxiogenic conditions [51,52].Since gestational hypoxia can have a long-lasting impact on offspring physiology, brain function, and behavior, it is important to understand the in uence of sex and age on gestational hypoxia-associated chronic outcomes.…”

“…Differences in steroid hormones, (e.g., testosterone, cortisol, estrogen) during gestation and later in life may also contribute to the phenotype of ASD [44][45][46][47][48]. The intensity of social impairments, repetitive behaviors, and precocious puberty in ASD has been correlated to testosterone and estradiol levels [27,49,50]. Further, elevated diurnal cortisol may contribute to comorbid anxiogenic conditions [51,52].…”

Pathogenic/likely pathogenic mutations identified in Vietnamese children diagnosed with autism spectrum disorder using high-resolution SNP genotyping platform

“…Sanger Sequencing or ARMS PCR). There are variations in genes previously strongly associated with ASD such as SLCO1B1 26 , ACADSB 27 , TCF4 28 , HCP5 29 , MOCOS 30 , SRD5A2 31 , MCCC2 32 , DCC 33 and PRKN 34 . The ratio of males/ females among the samples with identified mutations is 3.93 (Sup.…”

“…Table 4 ). In terms of SRD5A2 , a recent study found that ASD boys with rs9282858 mutation in this testosterone metabolism-related gene showed higher levels of restricted and repetitive behaviors 31 . In addition, multiple recent studies published on Clinvar have consistently concluded SRD5A2 rs9332964 as pathogenic/likely pathogenic.…”