Session: 6

PS6-09 | Neonatal exposure to 17beta-estradiol results on impairment in social habituation in adult females prenatally exposed to valproic acid

Araceli Seiffe


Autism spectrum disorders (ASD) are characterized by reduced sociability, diminished communicative skills and repetitive behaviors. Notably, the proportion between boys and girls diagnosed with ASD is about 4 to 1. To identify the biological mechanisms involved in this bias, we use a mouse model of ASD: the prenatal exposure to valproic acid (VPA). Recently, we observed that females do not show the reduction in sociability observed in adult males. Our hypothesis is that the masculinization process that male brains experience during development, due to the early exposure to gonadal hormones, is necessary for prenatal VPA exposure to affect autism-related behaviors.
To test this hypothesis, we studied the effect of neonatal exposure to 17β-estradiol benzoate (E2) in female mice of the VPA model. We carried out an comprehensive behavioral analysis of these animals. In the habituation and novelty recognition task, we observed that only VPA-E2 females failed to habituate to the stimulus mouse. We also found that E2 exposure results in reduced immobility in the forced swim test and a lower latency to approach the food in the novelty suppressed feeding.
E2 treatment was sufficient to alter the normal development of secondary sex characteristics, as ovaries of E2 females weighed less than those of OIL females.
Further studies of the VPA-E2 mice could help us identify possible biological mechanisms underlying the behavioral effects of both VPA and masculinization.