Fentanyl and fentanyl-xylazine co-exposure influence mitochondrial transcriptional programs in human trophoblasts

Fentanyl exposure suppresses mitochondrial and ribosomal transcriptional programs in human trophoblast syncytiotrophoblasts (STBs), consistently across 4-day and 9-day durations.

• Why it matters: Illicit fentanyl during pregnancy is linked to adverse outcomes, but its direct molecular effects in human trophoblasts—and how adulterants like xylazine or medetomidine contribute—remain unclear.
• What they did: Human trophoblast stem cells were differentiated into TS-CTBs and STBs, then exposed for 4 days or 9 days to fentanyl alone or combined with medetomidine and xylazine (FMX), followed by transcriptional profiling and temporal pathway analysis.
• The result: FMX co-exposure over 9 days altered mitochondrial respiratory chain gene expression in STBs, producing discordant regulation between nuclear and mitochondrial genome-encoded genes and indicating progressive mitochondrial transcriptional dysregulation.

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