Early life stress

Epigenetic mechanisms involve chemical modifications of the DNA (e.g., DNA methylation) or proteins compacting it (e.g., histones). These modifications can regulate gene expression and be maintained after cell divisions. Epigenetic inheritance describes the maintenance of epigenetic patterns after cell divisions (mitotic inheritance) or the consequences of epigenetic changes (generally in the germ line) across generations (transgenerational inheritance). Several factors are among the environmental influences reported to interfere with epigenetic programming during early development, among them endocrine disrupting or inorganic chemicals, nutritional compounds, or stressful conditions. Early developmental exposure to endocrine disruptors is shown to affect reproduction and metabolism in the subsequent generations in rodents. Stress have also been reported to produce developmental and transgenerational effects in animal models, including mammals and chickens. Importantly, these epigenetic modifications are detected both in the CNS and in peripheral cells. Because in birds red blood cells are nucleated, unlike in mammals, and sperm collection can be performed without sacrificing the animal, the chicken model provides unique features to perform longitudinal and transgenerational studies on the effects of stress. Stress often does not only affect individuals and organisms directly exposed but can also have an impact on the progeny`s health. It can thereby potentially explain in part the missing heritability of disease that evolves around the fact that many complex diseases have a strong heritable component that cannot be attributed to single genetic factors. We and others have described a range of behavioral and metabolic effects of early life stress on the male line offspring in mice. We pinpointed specific epigenetic alterations including DNA methylation, histone post translational modifications and small and long non-coding RNA in the brain and the germline as mediators. We have recently identified an interesting contribution of circulating blood metabolites in the induction of crucial germline alterations that was also reflected in a cohort of children exposed to early life stress. This indicates that our findings are potentially also relevant to human disease risk heritability. Essential hypertension is a complex condition of unknown pathogeneses. Recent advances in the field of developmental origins of increased blood pressure add another layer of complexity. Complications during pregnancy that program increased blood pressure in the offspring are varied and can include preeclampsia, parental smoking or alcohol consumption, maternal stress, or poor perinatal nutrition. Low birth weight serves as a crude proxy for impaired fetal growth indicative of intrauterine growth restriction (IUGR) and numerous experimental models of IUGR are utilized to examine the link between adverse events in early life and increased cardiovascular risk. These experimental models provide proof of principle that birth weight is inversely associated with blood pressure and indicate that despite the method of maternal/fetal insult, mutual mechanistic pathways contribute to the etiology of increased blood pressure in IUGR offspring. The renin angiotensin system, the sympathetic nervous system, endothelin, oxidative stress and vascular dysfunction are all implicated as contributors to increased blood pressure that has its origins in early life. Sex and age also effect the long-term consequences of IUGR on blood pressure control.