Maternal rejecting of newborns is epigenetic, intergenerationally transmitted and associated with altered miRNAs expression in owl monkeys.

Spontaneous maternal rejection of offspring is a considered a behavioural pathology affecting human and non-human primates, often with lethal consequences for newborns, yet it is widespread and pervasive across taxa, induced by stress or stress vulnerability. In some species, events of rejection can trigger chains of rejection which replicate themselves through generations. In this study we hypothesized that rejecting behaviours in owl monkeys are triggered and epigenetic in nature, transmitted to descendants, and their manifestation is associated with altered miRNA expression. Analysis of multi-generational records revealed that individuals who experienced rejection in infancy were 1.9 times more likely to reject their own offspring compared to controls, confirming its triggered nature. Transmission appears induced by experience rather than solely explained by genetic relatedness, as non-rejected full siblings showed no increased rejection tendency. Transcriptomic analysis identified distinct microRNA signatures associated with epigenetically induced rejecting behaviours. In rejected adults that become rejectors of their own offspring, mml-miR-1296, involved in lipid metabolism was significantly downregulated. In the naive daughters of rejected-rejectors, upregulated mml-miR-125b-5p, previously identified as biomarker in humans exposed to early life trauma that also suffered behavioural pathology, was identified. In summary, these findings confirm the epigenetic nature of spontaneous rejecting, with robust intergenerational transmission, and accompanied by alteration of epigenetic marks across generations in owl monkeys.