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Published on: July 13, 2014
Prenatal Opioid and Alcohol Exposures: Association with Altered Placental Serotonin Transporter Structure and/or
Nune Darbinian1, Nana Merabova1,2, Gabriel Tatevosian1
1Center for Neural Repair and Rehabilitation (Shriners Hospitals Pediatric Research Center), Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Insights
Prenatal exposure to opioids alters serotonin transporter (SERT) expression and function in the placenta, potentially impacting fetal neurodevelopment. Alcohol exposure reduces SERT levels, with both substances affecting fetal brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Fetal exposure to opioids and alcohol is linked to neurodevelopmental issues.
- Abnormalities in placental serotonin transporter (SERT) activity are implicated.
- Limited understanding exists regarding how these substances affect SERT expression.
Purpose of the Study:
- To investigate the impact of prenatal opioid and alcohol exposure on placental SERT expression and modifications.
- To identify novel SERT isoforms resulting from such exposures.
Main Methods:
- Comparison of placentas from pregnant women with and without reported opioid or alcohol use.
- Analysis of placental membranous vesicles and exosomes from first and second-trimester human placentas.
- Quantitative western blot and sequencing to assess SERT expression, cleavage, and isoform formation.
Main Results:
- Opioid-exposed placentas exhibited SERT cleavage and new fragment formation, not observed with alcohol.
- Alcohol-exposed placentas showed reduced overall SERT levels.
- Antibody binding indicated that cleavage products lack the N-terminal SERT region, suggesting specific modifications.
Conclusions:
- Opioid and alcohol exposure during pregnancy differentially alter placental SERT expression and modification.
- These placental changes may lead to altered fetal brain serotonergic neurotransmission.
- Further research is needed to understand the neurodevelopmental implications of these findings.
Abstract:
Fetal exposures to many drugs of abuse, e.g., opioids and alcohol (EtOH), are associated with adverse neurodevelopmental problems in early childhood, including abnormalities in activity of the serotonin (5HT) transporter (SERT), which transports 5HT across the placenta. Little is known about the effects of these drugs on SERT expression. Pregnant women who used EtOH or opioids were compared to gestational age-matched controls using a structured questionnaire to determine prenatal substance exposure. Following elective pregnancy termination, placental membranous vesicles and exosomes were prepared from first and second trimester human placentas. Changes in EtOH- or opioid-exposed placental SERT expression and modifications were assessed by quantitative western blot. Novel SERT isoforms were sequenced and analyzed. Opioid-exposed but not EtOH-exposed maternal placentas showed SERT cleavage and formation of new SERT fragments (isoforms). Alcohol-exposed cases showed reduced SERT levels. Antibodies to the N-terminal SERT region did not recognize either of the two cleavage products, while antibodies to the central and C-terminal regions recognized both bands. The secondary band seen in the opioid group may represent a hypophosphorylated SERT fragment. These changes in SERT modifications and expression may result in altered fetal brain serotonergic neurotransmission, which could have neurodevelopmental implications.
