Alterations in Sensitivity to Estrogen, Dihydrotestosterone, and Xenogens in B-Lymphocytes from Children with Autism Spectrum Disorder and Their Unaffected TwinsSiblings

Abstract EN

It has been postulated that androgen overexposure in a susceptible person leads to excessive brain masculinization and the autism spectrum disorder (ASD) phenotype.

In this study, the responses to estradiol (E2), dihydrotestosterone (DHT), and dichlorodiphenyldichloroethylene (DDE) on B-lymphocytes from ASD subjects and controls are compared.

B cells were obtained from 11 ASD subjects, their unaffected fraternal twins, and nontwin siblings.

Controls were obtained from a different cell bank.

Lactate dehydrogenase (LDH) and sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction levels were measured after incubation with different concentrations of E2, DHT, and DDE.

XTT/LDH ratio, representative of mitochondria number per cell, was calculated.

E2, DHT, and DDE all cause “U”-shaped growth curves, as measured by LDH levels.

ASD B cells show less growth depression compared to siblings and controls (P<0.01).

They also have reduced XTT/LDH ratios (P<0.01) when compared to external controls, whereas siblings had values of XTT/LDH between ASD and external controls.

B-lymphocytes from people with ASD exhibit a differential response to E2, DHT, and hormone disruptors in regard to cell growth and mitochondrial upregulation when compared to non-ASD siblings and external controls.

Specifically, ASD B-lymphocytes show significantly less growth depression and less mitochondrial upregulation when exposed to these effectors.

A mitochondrial deficit in ASD individuals is implied.