Faculty, Staff and Student Publications
Publication Date
10-28-2024
Journal
International Journal of Molecular Sciences
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.
Keywords
Humans, Serotonin Plasma Membrane Transport Proteins, Pregnancy, Female, Placenta, Ethanol, Adult, Analgesics, Opioid, Prenatal Exposure Delayed Effects, Protein Isoforms, placental transport, FASD, suboxone, subutex, methadone, vesicles, exosomes
DOI
10.3390/ijms252111570
PMID
39519122
PMCID
PMC11546934
PubMedCentral® Posted Date
10-28-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes