Distinct, sex-dependent miRNA signatures in piglet hippocampus induced by a clinically relevant isoflurane exposure: a pilot study

Purpose: To evaluate the effects of sex on miRNA expression in the hippocampus after isoflurane anesthesia in a neonatal piglet model. Methods: Six male and 6 female piglets, aged 3–5 days, were anesthetized with 2% isoflurane in room air for 3 h. Full physiologic monitoring was observed. Untreated animals (6 male, 6 female) served as controls. Expression of miRNAs in hippocampus was assessed. Results: In controls, miRNA expression in the hippocampus was highly conserved between males and females. However, 17/326 displayed sex-dependent differences: 10 miRNAs were more highly expressed in males; 7 showed lower expression in males than females. Isoflurane was associated with changes in the expression of distinct subsets of miRNAs in both males and females. In females, 14/326 miRNAs were significantly changed (3 downregulated; 11 upregulated); in males, 17/326 miRNAs were changed (7 downregulated; 10 upregulated). There was no overlap in significantly changed miRNAs between isoflurane-exposed males and females. Conclusions: In the neonatal piglet hippocampus, miRNA expression was highly conserved. There was no overlap in miRNA expression between isoflurane-exposed males and females, suggesting sex differences in isoflurane-induced miRNA expression. These results support the hypothesis that a clinically relevant exposure to isoflurane induces distinct miRNA signatures in the hippocampus of neonatal male and female piglets. Their functional relevance in anesthesia-induced neurotoxicity remains unknown, although changes in specific miRNAs may either contribute to or protect against anesthesia-induced neurotoxicity.