Phenotypic plasticity: historical context, theories and DOHaD

The Developmental Origins of Health and Disease (DOHaD) concept has emerged as an interdisciplinary framework that explores how early-life events shape long-term health and disease risk. Rooted in the Thrifty Phenotype hypothesis proposed by Barker and Hales, DOHaD builds upon centuries of philosophical and scientific thought. Central to DOHaD is the concept of phenotypic plasticity, which explains how organisms adapt their biological characteristics in response to environmental stimuli, particularly during critical developmental periods. In this context, this review aims to analyze the historical evolution of phenotypic plasticity, its theoretical foundations, and its role in health and disease. After reviewing the literature on scope, we summarize key contributions from evolutionary biology, genetics, and epigenetics, examining theories from Lamarck, Darwin, Mendel, and Waddington to contemporary perspectives in DOHaD. Understanding that early-life events can lead to adaptations which may have short-term benefits but potentially increase the likelihood of diseases in adulthood highlights the importance of targeted preventive interventions. Additionally, individual variations in response to environmental stimuli reinforce the complexity of adaptive mechanisms. Thus, understanding the intricate relationship between phenotypic plasticity, early-life exposures, and disease risk is essential for developing preventive interventions and public health strategies. The challenge remains in translating these findings into effective healthcare policies and clinical applications, ensuring improved quality of life and disease prevention across generations.