Autistic-like behavioral effects of prenatal stress in juvenile Fmr1 mice: the relevance of sex differences and gene-environment interactions.

Researchers studied how stress during pregnancy affects autism-like behaviors in mice with Fragile X Syndrome, a genetic condition that often causes autism. They found that prenatal stress made memory problems appear earlier in male mice with the genetic condition, but affected females differently. This shows that environmental stress during pregnancy can interact with genetic factors to influence when autism-related behaviors develop, and that males and females may be affected differently.

This study examined how prenatal stress affects autism-like behaviors in young mice with Fragile X Syndrome (FXS), the most common genetic cause of autism. Researchers exposed pregnant mice to stress and tested their offspring at 7-8 weeks old using a mouse model that lacks the FMR1 gene. Results showed that prenatal stress caused male mice with the genetic mutation to develop memory problems earlier than expected, while females were less affected. Stress also influenced social interaction and communication differently between males and females, and between mice with and without the genetic mutation.

The findings highlight how environmental factors like prenatal stress can interact with genetic vulnerabilities to influence when and how autism-like behaviors appear, with important sex differences in these effects.

Findings suggest prenatal stress may be a risk factor that interacts with genetic vulnerabilities to influence autism symptom development. Sex differences indicate males and females may have different sensitivities to prenatal environmental factors. This supports the importance of prenatal care and stress reduction during pregnancy, particularly for families with genetic autism risk factors.

Study used animal models which may not fully translate to humans. Sample size not reported. Behavioral testing limited to one age point (7-8 weeks). Long-term effects not assessed. Specific stress protocols and behavioral measures not detailed in abstract.

Fragile X Syndrome (FXS) is the most common heritable form of mental retardation and monogenic cause of autism spectrum disorder (ASD). FXS is due to a mutation in the X-linked FMR1 gene and is characterized by motor, cognitive and social alterations, mostly overlapping with ASD behavioral phenotypes. The severity of these symptoms and their timing may be exacerbated and/or advanced by environmental adversity interacting with the genetic mutation. We therefore tested the effects of the prenatal exposure to unpredictable chronic stress on the behavioral phenotype of juveniles of both sexes in the Fmr1 knock-out (KO) mouse model of FXS.

Mice underwent behavioral tests at 7-8 weeks of age, that is, when most of the relevant behavioral alterations are absent or mild in Fmr1-KOs. Stress induced the early appearance of deficits in spontaneous alternation in KO male mice, without exacerbating the behavioral phenotype of mutant females. In males stress also altered social interaction and communication, but mostly in WT mice, while in females it induced effects on locomotion and communication in mice of both genotypes. Our data therefore highlight the sex-dependent relevance of early environmental stressors to interact with genetic factors to influence the appearance of selected FXS- and ASD-like phenotypes.