REVIEW ARTICLE Sexual Dimorphism in Non-Mendelian Inheritance

There is accumulating evidence for nongenetic trans- generational inheritance with conspicuous marked sexual dimor- phism for both the modes of transmission and the effects. Given the critical spatiotemporal windows, the role of the sex chromosomes, the regulatory pathways underlying sexual differentiation during gonad and brain development, and other developmental processes, as well as the lifelong impact of sex hormones, it is not surprising that most of the common diseases, which often take root in early devel- opment, display some degree of sex bias. The flexibility of epigenetic marks may make it possible for environmental and nutritional factors, or endocrine disruptors to alter— during a particular spatiotemporal window in a sex-specific manner—the sex-specific methylation or demethylation of specific CpGs and histone/chromatin modifications underlying sex-specific expression of a substantial proportion of genes. Thus, finely tuned developmental program aspects, specific to one sex, may be more sensitive to specific environmental challenges, particularly during developmental programming and gametogenesis, but also throughout the individual's life under the influence of sex steroid hormones. This review highlights the importance of studying both sexes in epidemiologic protocols or dietary interventions both in humans and in experimental models in animals. (Pediatr Res 63: 340-347, 2008)