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Effects of prenatal opioid and alcohol exposures on immune and serotonin factors in human placenta.

Authors
  • Ruyak, Sharon L1
  • Noor, Shahani2
  • DiDomenico, Jared3
  • Sun, Melody S2
  • Fernandez Oropeza, Annette K2
  • Rodriguez, Dominique E3
  • Marquez, Lidia Enriquez3
  • Milligan, Erin D2
  • Bakhireva, Ludmila N3
  • 1 College of Nursing, University of New Mexico Health Sciences Center, Albuquerque, NM, United States of America; College of Pharmacy Substance Use Research Education Center, University of New Mexico Health Sciences Center, Albuquerque, NM, United States of America. Electronic address: [email protected] , (Mexico)
  • 2 Department of Neurosciences, University of New Mexico, Health Sciences Center, Albuquerque, NM, United States of America. , (Mexico)
  • 3 College of Pharmacy Substance Use Research Education Center, University of New Mexico Health Sciences Center, Albuquerque, NM, United States of America. , (Mexico)
Type
Published Article
Journal
Experimental Neurology
Publisher
Elsevier
Publication Date
Mar 29, 2022
Volume
353
Pages
114057–114057
Identifiers
DOI: 10.1016/j.expneurol.2022.114057
PMID: 35364108
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Opioids and alcohol impact critical serotonin (5-HT) function in the developing placenta and fetus through the actions of immune proinflammatory factors. Yet, possible convergent effects of opioids and alcohol on human placental toll-like receptor 4 (TLR4) activation and subsequent 5-HT homeostasis remain entirely unknown. The purpose of this study was to examine the effect of prenatal exposure to opioids with or without prenatal alcohol exposure (PAE) on the expression of key placental immune and serotonin signaling factors in human placental tissue obtained from a well-characterized prospective cohort. Data were collected from a subset of participants enrolled in the prospective pre-birth Ethanol, Neurodevelopment, Infant, and Child Health (ENRICH-1) cohort. Women were recruited and classified into four study groups: 1) PAE (n = 20); 2) those taking medications for opioid use disorder (MOUD; n = 28), 3) concurrent PAE and MOUD (n = 20); and 4) controls (HC; n = 20) based on prospective, repeated self-report, and biomarker analysis. Placenta samples underwent tissue processing to identify mRNA for TLR4, nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), serotonin transporter (SERT), tryptophan hydroxylase (TPH1), indoleamine 2,3-Dioxygenase 1 (IDO) as well as protein concentrations of TLR4, IL-1β, TNF-α, SERT. To consider the association between study group and mRNA/protein expression of our targets, multivariable regression models were developed with inclusion of a priori selected covariates. There was a significant negative association between PAE and SERT mRNA (β = -0.01; p < 0.01) and a positive association with TPH1 mRNA expression (β = 0.78; p < 0.05). In addition, there was a negative association between MOUD and TNF-α protein expression (β = -0.12; p < 0.05). This study provides the first evidence that PAE may inhibit SERT expression while simultaneously promoting increased TPH1 protein expression in human placenta. This may result in increased 5-HT in fetal circulation known to affect neurodevelopment. Our data suggest that opioids and alcohol may disturb the bidirectional, dynamic interaction between the placental immune and serotonin system. Given the implication for brain development and health across the life-span further investigation of these critical mechanisms in well-defined cohorts is required. Copyright © 2022 Elsevier Inc. All rights reserved.

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