NON-CODING RNA CHANGES IN ADOLESCENT STRESS-EXPOSED FEMALE RATS AND THEIR OFFSPRING

Pre-reproductive stress during adolescence induces long-lasting behavioral and molecular alterations and can affect subsequent generations. Transfer RNAs (tRNAs) and their fragments (tRFs) have recently emerged as regulators of stress responses and epigenetic inheritance. Here, we investigated whether chronic unpredictable stress (CUS) during adolescence alters tRNA/tRF profiles in the brain of female rats and their offspring, alongside changes in small non-coding RNAs (sncRNAs) in peripheral tissues and the germline.

Adolescent females were exposed to 7 days of CUS. tRNA and tRF expression was examined in the prefrontal cortex (PFC) of directly exposed females (4 and 14 days post-stress) and in their F1 neonate offspring using YAMAT-seq. In parallel, sncRNA profiles in blood and oocytes from stressed females were assessed using small RNA sequencing and RT-PCR.

CUS induced robust alterations in specific tRNA isodecoders and tRFs in the maternal PFC. Notably, while no changes in full-length tRNAs were detected in the F1 offspring, they exhibited the same specific tRF alterations observed in their mothers. In peripheral tissues, stress significantly altered miRNA levels in blood without affecting tRFs. Preliminary analyses further suggest differential miRNA expression in oocytes, indicating tissue-specific sncRNA responses to stress.

Together with our previous findings, these results suggest that adolescent stress reshapes miRNA and tRNA/tRF expression in a tissue-dependent manner and that germline and peripheral sncRNA alterations may contribute to the intergenerational transmission of stress-related effects.