Developmental processes affect the risk of a wide range of important non-communicable diseases and can partly explain the increased prevalence of important diseases over recent decades. Diseases that have serious implications for public health include heart disease, obesity and type 2 diabetes, certain cancer types, and dysfunction of the reproductive, neurocognitive and immune systems, all of which may have a substantial economic and societal impact.
One important example is obesity that has globally increased in prevalence. Feeding behaviour, satiety, energy metabolism, and glucose/insulin sensitivity are examples of a complex interacting control system that involves the brain, adipose tissue, the gastrointestinal tract, muscle, liver, and the pancreas, all of which are connected by neurohumoral processes, and for which the integrated control is established in part during early development.
Unbalanced nutrition in utero, associated with either under- and over-nutrition, can result in increased rates of obesity later in life. A high maternal pre-pregnancy BMI has been linked to increased gestational weight gain, with increased birth weight and fat mass at birth. Maternal gestational diabetes is also associated with increased birth weight as well as childhood risks of overweight and obesity and, later, of diabetes. Interestingly, paternal nutrition has also been linked to adverse health outcomes in offspring in animal models, e.g., paternal obesity can lead to disrupted insulin secretion and glucose tolerance in offspring. Furthermore, the developmental disruption can be subtle: maternal nutritional status can affect the offspring epigenetic states and body composition development independently of birth weight; first-born children are more likely to develop obesity and hypertension as adults in part because of greater maternal constraint in first pregnancies slightly reducing fetal growth and thus leading to greater potential mismatch.
Exposure to environmental chemicals has also been shown to result in increased risk of obesity later in life. These chemicals are referred to as obesogens. There are now about 20 chemicals and chemical classes that are known to lead to increased risk of weight gain later in life after developmental exposure and many of these same chemicals can also increase insulin resistance leading to type 2 diabetes, either concurrently with the obesity or independent of weight gain (examples include phthalates, bisphenol A, tributyltins, and several pesticides).
Other data indicate that developmental exposures to environmental chemicals can interact with unbalanced nutrition leading to aspects of metabolic syndrome later in life, indicating that both nutrient and chemical exposures can affect epigenetic processes controlling weight gain, metabolism and glucose tolerance. Indeed the “perfect storm” for obesity could be an interaction between unbalanced nutrition and environmental chemical exposures during development altering the set-point for weight gain and metabolism via effects on adipose tissue deposition, pancreas, muscle, gastrointestinal tract, liver and brain functions. This altered metabolism could be continually worsened by mismatched environmental exposures throughout life along with high fat and sugar diets as well as insufficient exercise.
Development of the human reproductive system begins toward the end of the first trimester; studies have shown its sensitivity to environmental chemicals, especially EDCs. A variety of dysfunctions and diseases, such as cryptorchidism, low semen quality, subfecundity, polycystic ovarian syndrome, testicular cancer, and uterine fibromyoma, have been linked to developmental exposures to EDCs. Unbalanced nutrition and growth during development can also lead to changes in reproductive function, e.g., the timing of puberty and fecundity.
Brain development involves complex developmental stages that must happen at a particular time and sequence. Disruption of a developmental process can lead to permanent damage that may be reflected in cognitive deficits, emotional or behavioural change. These changes may have important consequences in terms of lifetime income, delinquency risks or later development of degenerative nervous system disease. The mechanisms of induction of such adverse neurobehavioral outcomes are unclear and may involve neuron or progenitor cell toxicity, endocrine disruption, and other mechanisms brought about either by nutritional stressors or toxicant exposures. Epigenetic mechanisms relating developmental stress, nutrition and/or environmental chemicals, to behaviour and neuroendocrine function have been implicated in both animal and human studies.
The immune system undergoes important maturation during early postnatal development. As originally reflected in the so-called ‘hygiene hypothesis’, the recognition of foreign antigens after parturition allows proper detection of and protection against invading micro-organisms and against cells with an abnormal phenotype. If this developmental exposure does not happen optimally, adverse consequences may include allergy, autoimmune disease, inflammation and cancer. Again, the importance of developmental exposures has been documented, but not the specific role of nutritional imbalance or individual environmental chemicals, or their molecular mechanisms.
The examples above illustrate that developmental exposures to nutrients and environmental chemicals may have profound effects on organ functions and disease risks in later life. The risk factors also include tobacco smoke, drugs, and psychosocial stress. The overall impact of these factors, along with nutrients and environmental chemicals on the incidence of dysfunctions and non-communicable diseases, is likely to be substantial.
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