LAUSR

PURPOSE Hormonal imprinting is taking place perinatally at the first encounter between the developing hormone receptors and their target hormones. However, in this crucial period when the developmental window for physiological imprinting is open, other molecules, such as synthetic hormones and endocrine disruptors can bind to the receptors, leading to faulty imprinting with life-long consequences, especially to the immune system. This review presents the factors of stress and faulty hormonal imprinting that lead to reprogramming of the immune system. METHODS Relevant publications from Pubmed since 1990 were reviewed and synthesized. FINDINGS The developing immune system is rather sensitive to hormonal effects. Faulty hormonal imprinting is able to reprogram the original developmental program present in a given cell, with lifelong consequences, manifested in alteration of hormone binding by receptors, susceptibility to certain (non-infectious) diseases, and triggering of other diseases. As stress mobilizes the hypothalamic-pituitary-adrenal axis if it occurred during gestation or perinatally, it could lead to faulty hormonal imprinting in the immune system, manifested later as allergic and autoimmune diseases or weakness of normal immune defenses. Hormonal imprinting is an epigenetic process and is carried to the offspring without alteration of DNA base sequences. This means that any form of early-life stress alone or in association with hormonal imprinting could be associated with the developmental origin of health and disease (DOHaD). As puberty is also a period of reprogramming, stress or faulty imprinting can change the original (developmental) program, also with life-long consequences. IMPLICATIONS Considering the continuous differentiation of immune cells (from blast-cells) during the whole life, there is a possibility of late-imprinting or stress-activated reprogramming in the immune system at any periods of life, with later pathogenetic consequences. (Clin Ther. 2020; 42:XXX-XXX) © 2020 Elsevier Inc.