High Level Exposure of Testosterone During Mouse Pregnancy Impairs the Offsprings’ Social Behavior by Interrupting Neurexin-Neuroligin Binding

Background/Objectives: The onset of autism spectrum disorder (ASD) are thought to be related to the fetal testosterone (TSTN) level or binding of neurexin (Nrxn) and neuroligin (Nlgn) in distinct researches. However, their molecular mechanisms have yet to be re-vealed. We indicated that highly concentrated TSTN interrupts Nrxn-Nlgn binding in the neonate brain, causing impaired social behavior. Methods: We reproduced high concen-tration of TSTN in the womb by injecting TSTN to pregnant mice, followed by the quanti-fication of Nrxn-Nlgn binding in their neonate brain. We also explored the sociability and the social novelty preferences in the male or female offsprings. Results: Nrxn-Nlgn bind-ing was reduced by TSTN injection in the neonate brain. Furthermore, male mice showed impairment in social novelty, whereas female mice showed impairments in both social novelty and sociability by TSTN injection. Conclusions: In this study, we revealed that high concentration of TSTN during the brain development interrupted Nrxn-Nlgn binding and led to impairments in social behavior. The social behaviors of the offsprings were very similar to the symptoms of ASD. Thus, we uncovered the heretofore unknown mechanism of ASD to fill a gap between TSTN level and Nrxn-Nlgn binding.