title: An epigenetic basis for autism spectrum disorder risk and oral contraceptive use.
abstract: In the United States 1 in 68 children are diagnosed with autism spectrum disorder (ASD). Although the etiology is unknown, many scientists believe ASD is caused by a combination of genetic and environmental factors and/or epigenetic factors. The widespread use of oral contraceptives is one environmental risk factor that has been greatly overlooked in the biomedical literature. Oral contraceptives, synthetic hormones created to imitate natural human hormones and disrupt endogenous endocrine function to inhibit pregnancy, may be causing the harmful neurodevelopmental effects that result in the increased prevalence of ASD. It is conceivable that the synthetic hormones repeatedly assault the oocyte causing persistent changes in expression of the estrogen receptor beta gene. Ethinylestradiol, a known endocrine disruptor, may trigger DNA methylation of the estrogen receptor beta gene causing decreased mRNA resulting in impaired brain estrogen signaling in progeny. In addition, it is possible the deleterious effects are transgenerational as the estrogen receptor gene and many of its targets may be imprinted and the methylation marks protected from global demethylation and preserved through fertilization and beyond to progeny generations. This article will delineate the hypothesis that ethinylestradiol activates DNA methylation of the estrogen receptor beta gene causing decreased mRNA resulting in diminished brain estrogen signaling in offspring of mothers exposed to oral contraceptives. Considering the detrimental epigenetic and transgenerational effects proposed, it calls for further study.
authors.affiliation: Graduate School at the University of Alabama at Birmingham, UAB School of Public Health, 1665 University Blvd. # Rpjb22a, Birmingham, AL 35233, United States. Electronic address: kstrifert@uab.edu.
authors.forename: Kim
authors.initials: K
authors.lastname: Strifert
mesh_terms: D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics*; D003276:Contraceptives, Oral / Q000009:adverse effects*; D019175:DNA Methylation; D002658:Developmental Disabilities / Q000209:etiology; D044127:Epigenesis, Genetic; D047629:Estrogen Receptor beta / Q000235:genetics; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008745:Methylation; D008962:Models, Theoretical; D011247:Pregnancy; D015995:Prevalence; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D003276:Contraceptives, Oral; D047629:Estrogen Receptor beta; D004967:Estrogens; D012333:RNA, Messenger