Abstract
Female survivors of physical or psychological violence, including sexual violence, report significant long-term consequences defined as post-traumatic stress disorder (PTSD). Among these, depression, affective difficulties, anomalous behaviours, and worsened reproductive health may also affect offspring through transgenerational transmission involving primordial germ cells (PGCs) and/or through social transmission and acquisition of behavioural patterns from parent(s) to children. The concept of epigenomic modification involves several molecular targets that are sensitive to environmental stressors, which tune gene activity and expression. DNA methylation, histone acetylation, ncRNAs, telomere attrition, and mitochondrial dysfunction cooperate in maintaining homeostasis and may affect genes involved in key pathways, such as the hypothalamic–pituitary–adrenal axis, mediating the integrated homeostatic response to stressors. The most investigated genes were those implicated in neuroendocrine stress responses; dopamine, norepinephrine, and serotonin signalling; apoptosis; insulin secretion; neuroplasticity; reproduction; foetal growth; and cancer (e.g. MAOA, BRSK2, ADCYAP1, BDNF, DRD2, IGF2, H19). Additional investigated genes were those involved in other important functions, such as neuropeptide binding, immunoregulation, histone deacetylase/demethylase, inflammatory response, and serotonin uptake, yielding interesting but preliminary or not completely replicated findings (e.g. CRHR1, FKBP5, KDM1A, NR3C1, PRTFDC1, and SLC6A4). The assumption that epigenetic traits induced by negative experiences can be reversed by appropriate social, psychological, and pharmacological interventions has prompted the scientific community to investigate the relationship between epigenetic mechanisms and physical and psychological violence. This can help to identify direct links or epigenetic marks useful for optimizing personalized interventions encompassing the genetic, neuropsychiatric, social, and forensic medicolegal fields. Future research should be conducted with extreme caution to evaluate the long-term effects of such strategies and assess whether the immediate observed effects are maintained.
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; Villanova, Matteo 2 ; Scarpellini, Fabio 3 ; Milani, Daniela 4 ; Cecchi, Rossana 5 ; Singh, Ajay Vikram 6 ; Gaudio, Rosa Maria 7 ; Tisato, Veronica 8 1 Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; University Strategic Centre for Studies on Gender Medicine, University of Ferrara, 44121 Ferrara, Italy; Centre Haemostasis & Thrombosis, University of Ferrara, 44121 Ferrara, Italy [email protected]
2 Department of Education Sciences, Roma Tre University, 00154 Rome, Italy
3 CERM-Hungaria, 00198 Rome, Italy
4 Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
5 Department of Biomedical, Metabolic and Neural Sciences, Institute of Legal Medicine, University of Modena, 41125 Modena, Italy
6 Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany
7 Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; University Strategic Centre for Studies on Gender Medicine, University of Ferrara, 44121 Ferrara, Italy; Section of Legal Medicine and LTTA Centre, University of Ferrara, 44121 Ferrara, Italy
8 Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; University Strategic Centre for Studies on Gender Medicine, University of Ferrara, 44121 Ferrara, Italy; LTTA Centre, University of Ferrara, 44121 Ferrara, Italy





