Developmental origin of chronic diseases: toxicological implication

摘要

Human epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exerts a profound influence on physiological function and risk of disease in adult life. The molecular, cellular, metabolic, endocrine and physiological adaptations to intrauterine nutritional conditions result in permanent alterations of cellular proliferation and differentiation of tissues and organ systems, which in turn can manifest by pathological consequences or increased vulnerability to chronic diseases in adulthood. Intrauterine growth restriction (IUGR) due to intrauterine development derangements is considered the important factor in development of such diseases as essential hypertension, diabetes mellitus, ischemic diseases of the heart, osteoporosis, respiratory, neuropsychiatric and immune system diseases.An early life exposures to dietary and environmental exposures can have a important effect on epigenetic code, resulting in diseases developed later in life. The concept of the "developmental programming" and Developmental Origins of Adult Diseases (DOHaD) has become well accepted because of the compelling animal studies that have precisely defined the outcomes of specific exposures.The environmental pollullutants and other chemical toxicants may influence crucial cellular functions during critical periods of fetal development and permanently alter the structure or function of specific organ systems. Developmental epigenetics is believed to establish "adaptive" phenotypes to meet the demands of the later-life environment. Resulting phenotypes that match predicted later-life demands will promote health, while a high degree of mismatch will impede adaptability to later-life challenges and elevate disease risk. The rapid introduction of synthetic chemicals, environmental pollutants and medical interventions, may result in conflict with the programmed adaptive changes made during early development, and explain the alarming increases in some diseases.