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Buprenorphine Induces Human Fetal Membrane Sterile Inflammation.
Biorxiv : the Preprint Server for Biology
|November 28, 2024
Summary
Buprenorphine, used to treat opioid-use disorder (OUD) in pregnancy, significantly increases inflammation and weakening factors in fetal membranes, potentially explaining the higher preterm birth risk associated with OUD. This research identifies key inflammatory pathways involved.
Area of Science:
- Reproductive biology
- Immunology
- Pharmacology
Background:
- Opioid-use disorder (OUD) in pregnancy is a growing concern, linked to increased maternal morbidity, mortality, and preterm birth.
- While medications like buprenorphine are recommended for OUD, the rate of preterm birth remains elevated in treated individuals compared to the general population.
- Placental and fetal membrane inflammation are known contributors to preterm birth.
Purpose of the Study:
- To investigate whether buprenorphine induces sterile inflammation in human fetal membranes (FM).
- To elucidate the underlying molecular mechanisms by which buprenorphine may affect FM integrity and contribute to preterm birth.
Main Methods:
- Utilized an established in vitro human FM explant system.
- Exposed explants to buprenorphine and measured the secretion of inflammatory cytokines (IL-6, IL-8, IL-1β), prostaglandin E2 (PGE2), and matrix metalloproteinases (MMP1, MMP9).
- Investigated the roles of Toll-like receptor 4 (TLR4), NLRP3 inflammasome, μ-opioid receptor, and downstream signaling pathways (NFκB, ERK/JNK/MAPK).
Main Results:
- Buprenorphine significantly increased the secretion of inflammatory mediators IL-6, IL-8, and IL-1β from human FMs.
- Exposure to buprenorphine elevated levels of PGE2, MMP1, and MMP9, factors associated with membrane weakening.
- The inflammatory and weakening response was partially mediated by TLR4, NLRP3 inflammasome, μ-opioid receptor, and NFκB/ERK/JNK/MAPK signaling pathways.
Conclusions:
- Buprenorphine induces sterile inflammation and weakening in human fetal membranes, potentially explaining the increased preterm birth risk in pregnant individuals with OUD.
- The findings highlight specific innate immune and signaling pathways involved in buprenorphine's effects on FMs.
- This research may inform strategies to mitigate the adverse pregnancy outcomes associated with OUD treatment, allowing continued essential maintenance therapy.
