Developmental Programming, a Pathway to Disease

Abstract

Accumulating evidence suggests that insults occurring during the perinatal period alter the developmental trajectory of the fetus/offspring leading to long-term detrimental outcomes that often culminate in adult pathologies. These perinatal insults include maternal/fetal disease states, nutritional deficits/excess, stress, lifestyle choices, exposure to environmental chemicals, and medical interventions. In addition to reviewing the various insults that contribute to developmental programming and the benefits of animal models in addressing underlying mechanisms, this review focuses on the commonalities in disease outcomes stemming from various insults, the convergence of mechanistic pathways via which various insults can lead to common outcomes, and identifies the knowledge gaps in the field and future directions.

Figure 1.

Impact of perinatal insults in programming adult pathologies in the offspring. Exposure of the fetus/offspring to different insults during critical periods of development may lead to adaptations that prove to be detrimental and associated with adult defects in several organ systems. IUGR, intrauterine growth restriction.

Figure 2.

Commonalities in the mechanisms through which different perinatal insults could lead to development of adult disorders. Different perinatal insults (disease states, environment, and lifestyle choices) by altering the epigenome/metabolome/microbiome, inflammatory/oxidative stress mechanisms, or endocrine signals have the potential to alter the fetal developmental trajectory culminating in adult disorders and may also serve as early biomarkers of future disease states.