Early Life Stress (ELS) Effects on Fetal and Adult Bone Development

Early life stress (ELS) refers to harmful environmental events (i.e., poor maternal health, metabolic restraint, childhood trauma) occurring during the prenatal and/or postnatal period, which may cause the 'epigenetic corruption' of cellular and molecular signaling of mental and physical development. While the impact of ELS in a wide range of human diseases has been confirmed, the ELS susceptibility to bone diseases has been poorly explored. In this review, to understand the potential mediating pathways of ELS in bone diseases, PRISMA criteria were used to analyze different stress protocols in mammal models and the effects elicited in dams and their progeny. Data collected, despite the methodological heterogeneity, show that ELS interferes with fetal bone formation, also revealing that the stress type and affected developmental phase may influence the variety and severity of bone anomalies. Interestingly, these findings highlight the maternal and fetal ability to buffer stress, establishing a new role for the placenta in minimizing ELS perturbations. The functional link between ELS and bone impairments will boost future investigations on maternal stress transmission to the fetus and, parallelly, help the assessment of catch-up mechanisms of skeleton adaptations from the cascading ELS effects.