Developmental origin of chronic diseases: toxicological implication

Abstract

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.

Exposure to phthalates, bisphenol A and metals in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC study

“…Although the causes of increasing rates of GDM are likely multifactorial, exposure to environmental chemicals may be partly responsible for this trend (Bezek et al, 2008;Kuo et al, 2013;Thayer et al, 2012). Some epidemiologic research has found associations between environmental chemicals and GDM (Ettinger et al, 2009;Saldana et al, 2007), but there have not been enough studies on this issue to draw definitive conclusions.…”

Fathers That Are Born Small Program Alterations in the Next-Generation Preimplantation Rat Embryos ,

“…Epidemiologic studies have highlighted that being born small is linked to increased disease risk, not only for that individual but also for subsequent generations (4,5). Proposed mechanisms include direct effects on germ cells in the first-generation (F1) 6 fetus by inheritance of persistent genetic or epigenetic modifications in a parent-specific manner or by abnormal pregnancy adaptations (6).…”

Complications during pregnancy and fetal development: implications for the occurrence of chronic kidney disease

“…Preeclampsia is one of the most common causes of fetal growth restriction in the United States, and its incidence has risen continually over the last three decades (21). However, other placental disorders, perinatal exposures to nicotine, other synthetic chemicals or environmental pollutants, chronic maternal illness or stress, and maternal infections are also associated with IUGR (18, 22, 23). Numerous epidemiological and experimental studies focus on the link between IUGR of different origins and the chronic health outcomes of offspring in later life.…”