Across studies, the ratio of male to female affected with autism is approximately 4:1. This striking sex difference has been seen consistently. Basic research on sex differences in behavior has shown that differences in circulating levels of gonadal hormones during fetal and infant development are responsible for most sexual dimorphism in adults. For normal male development to occur, sex hormones like testosterone act through estrogen receptors, which in turn also activate other genes and proteins. The activation of certain genes through estrogen receptor, then, may partially explain the sex difference. The body produces natural testosterone and estrogen that a normal body produces, but environmental chemicals may mimic these compounds and produce deleterious effects during development. For example, a chemical called Bisphenol A, has been used as a plasticzer agent and is found in beverage bottles, and other plastic products has several actions; as an estrogen agonist or antagonist, or as an anti-androgen and as a disruptor of hormone biochemical pathways. It is also a DNA hypomethylating agent and thus affects transcription of other genes. In the past year consensus statements from the scientific community express concern that this compound acts via a number of mechanisms on the brain during development. This study will use estrogen receptor knockout mice to determine sex-differences on many autism like behaviors in mice, and identifying genes which are affected by BPA, in order to identify the mechanism of action of this environmental chemical, and whether it may be linked to autism. What this means for people with autism: Dr. Rissman and her colleagues will not only explore the role of Bisphenol A in autism, but determine the mechanism by which sex hormones may interact with environmental agents during critical periods in development. It will also further explore the role that modifications of the “epigenome” may result in abnormal behaviors, opening the door for researchers examining other exposures of interest.