hsa-miR-582-3p in umbilical cord blood is negatively associated with maternal exposure to childhood maltreatment

<b>Aim:</b> Childhood maltreatment (CM) may affect not only directly exposed individuals but also their offspring. However, the underlying biological mechanisms remain unclear. microRNAs (miRNAs) may play a regulatory role in this process. This study investigates the relationship between maternal exposure to CM and miRNA expression in maternal and perinatal tissues. <b>Methods:</b> We enrolled 43 pregnant women and assessed their CM exposure. We collected maternal blood, cord blood and placental tissue samples during childbirth and performed miRNA profiling using next generation sequencing. <b>Results:</b> Maternal CM was inversely associated with hsa-miR-582-3p levels in cord blood. Pathway analysis revealed that this miRNA regulates genes involved in intrauterine development. <b>Conclusion:</b> Our findings highlight the potential impact of maternal CM exposure on offspring epigenetic mechanisms. Child maltreatment (CM) includes physical, sexual and emotional abuse, as well as physical and emotional neglect. CM not only harms those directly exposed but can also negatively impact their offspring. However, the biological reasons behind this are not well understood. To explore this further, our study investigates how CM affects the biology of pregnant women and their newborns through changes in small regulatory molecules called microRNAs (miRNAs). We recruited 43 pregnant women and assessed their exposure to CM. During childbirth, we collected blood samples from the mothers, blood from the umbilical cord and placental samples. We then analyzed the levels of miRNAs in these samples using advanced sequencing technology. We observed that more severe maternal exposure to CM was associated with lower levels of a miRNA named hsa-miR-582-3p in umbilical cord blood. This miRNA regulates genes involved in fetal development in utero and has been linked to spontaneous preterm birth. It may also influence immunologic and stress-related processes. Thus, newborns of mothers who had been exposed to CM may be more vulnerable to adverse effects on their brain development and overall health. Despite our small sample size, our study highlights the importance of addressing CM as an intergenerational concern and provides new insights into the biological mechanisms through which maternal CM can affect offspring. Child maltreatment (CM), encompassing physical, sexual and emotional abuse, as well as physical and emotional neglect, may affect not only directly exposed individuals but also their offspring. Epigenetic alterations, such as changes in miRNA expression profiles, may play a regulatory role in this process. We investigate the association between maternal CM and miRNA expression profiles in maternal peripheral blood, umbilical cord and placenta. We enrolled 43 women in the third trimester of a low-risk gestation and their newborns in the public maternity hospital in Brazil. We assessed maternal history to CM using the Childhood Trauma Questionnaire and exposure to recent abuse using the Abuse Assessment Screen. We collected the samples during childbirth and performed miRNA expression profiling using Next Generation Sequencing. Associations between maternal CM and miRNA expression were tested using linear regression models, controlling for potential covariates. miRNA target genes were predicted using miRwalk or TargetScan and enrichment for biological pathways was analyzed using the “gene2func” function of FUMA GWAS. hsa-miR-582-3p in umbilical cord blood is negatively associated with maternal history of CM. The enrichment analysis of target genes associated with hsa-miR-582-3p in GWAS for spontaneous early preterm birth and pathways related to embryonic development underlines its potential role in intrauterine development. 112 candidate miRNAs were identified in our data, although none were associated with maternal history of childhood maltreatment. The enrichment analyses showed important pathways for fetal development and point to the possible role of hsa-miR-582-3p as a molecular regulator during this period. Possibly, the altered profile of this miRNA could render the newborns an altered physiology, which could be contributing to the impact on offspring's health associated with maternal history of CM. To our knowledge, this is the first study to identify in humans changes in offspring's miRNA expression associated with maternal exposure to CM. hsa-miR-582-3p has significant negative correlation with maternal exposure to CM in umbilical cord blood. Pathway enrichment analysis of hsa-miR-582-3p target genes pointed to their roles in important pathways for fetal development. Despite the limitations imposed by our sample size, our study provides valuable insights into the potential impact of maternal CM exposure on offspring epigenetic mechanisms.