INTRODUCTION: Childhood trauma has been associated with long-term behavioral and metabolic sequelae across generations. Emerging evidence from rodent studies supports a role for sperm RNAs in the intergenerational transmission of neuropsychiatric and metabolic disease susceptibilities through the patriline. However, the translational relevance of this concept in humans remains understudied.  

AIM(S): We systematically examined small RNAs in the serum and sperm samples from different human trauma cohorts to synthesize evidence for the plausibility of intergenerational transmission of susceptibilities in humans. These include Pakistani children (n=72, n=42 controls) and adult men (n=93) with histories of complex childhood trauma, as well as Bosnian families (n=22, n=20 controls) who lived through the genocide during their formative years.

METHOD(S): Small RNA sequencing (sRNA-seq) followed by RT-qPCR assays were performed in the collected serum and sperm samples from the Pakistani and Bosnian trauma cohorts. The data was compared and correlated with the neuropsychiatric scales and lipid profiles of the subjects intergenerationally.

RESULTS: sRNA-seq revealed differential expression of 48 miRNAs in the serum of traumatized children vs. controls in Pakistan, whereas 29 miRNAs are altered in the sperm of trauma-exposed Pakistani men compared to controls. Similarly, a number of miRNAs were differentially expressed in the sperm of Bosnian men exposed to genocide. Importantly, neuropsychiatric symptoms in the Bosnian children correlated with miRNAs expression in the sperm of their fathers.  

CONCLUSIONS: Collectively, these findings underscore the potential role of serum and sperm miRNAs in the intergenerational transmission of trauma-related phenotypes in humans and support the candidacy of certain miRNAs as biomarkers of such effects. 

FINANCIAL SUPPORT: SONATA, MUSE ACE grants