Intergenerational Memories of Past Nutritional Deprivation: The Phenotypic Inertia Model

Abstract

Human and animal model research shows that prenatal nutrition influences early development and has long-term effects on adult biology and chronic disease. Much of this literature has emphasized the limited maternal capacity to buffer the fetus from stressors that negatively impact development. An alternative perspective recognizes that a subset of prenatal biological responses reflect an ability to adaptively change how the body regulates metabolism, hormone production, and other biological functions in anticipation of postnatal environmental conditions. The applicability of this concept to humans has been challenged on the basis of the long duration of the human life span and the imperfect correlation between environmental conditions during early and later life. The phenotypic inertia model proposes a solution to this problem: if maternal physiology and metabolism transfer nutrients or hormones in relation to the mother’s average life experience, rather than to the specific conditions experienced during that pregnancy, this could provide a more reliable basis for the fetus to adjust its long-term strategy. This hypothesis is supported by evidence that fetal nutrition is buffered against short-term fluctuations in maternal intake during pregnancy in women who are not on the extreme ends of energy balance, while showing evidence of sensitivity to a mother’s early developmental and chronic nutritional experience. Maternal buffering of fetal nutrition in humans is predicted to limit the deleterious impact of nutritional stress experienced by the mother during pregnancy while also attenuating the long-term health benefits of short-term dietary supplements consumed during pregnancy. According to this model, maternal interventions aimed at improving the health of future generations via fetal nutritional programming will be most effective when they emulate sustained, rather than transient, nutritional improvement.