title: Placental Mitochondrial Toxicity, Oxidative Stress, Apoptosis, and Adverse Perinatal Outcomes in HIV Pregnancies Under Antiretroviral Treatment Containing Zidovudine.
abstract: To determine whether mitochondrial, oxidative, and apoptotic abnormalities in placenta derived from HIV and combined antiretroviral therapy (cART) containing zidovudine (AZT) could be associated with adverse perinatal outcome.
  
  
  
  Cross-sectional, controlled, observational study.
  
  
  
  We studied obstetric results and mitochondrial, oxidative, and apoptotic state in placenta of 24 treated HIV-infected and 32 -uninfected pregnant women. We measured mitochondrial DNA (mtDNA) content by quantitative reverse transcriptase-polymerase chain reaction (mtND2/n18SrRNA), oxidative stress by the spectrophotometric quantification of lipid peroxidation and apoptosis by Western blot analysis of active caspase-3 respect to β-actin content and analysis of the terminal deoxynucleotidyl transferase dUTP nick end labeling.
  
  
  
  Global adverse perinatal outcome (defined as preterm delivery or/and small newborns for gestational age) was significantly increased in HIV pregnancies [or 6.7 (1.3-33.2); P < 0.05]. mtDNA content in HIV-infected women was significantly depleted (39.20% ± 2.78%) with respect to controls (0.59 ± 0.03 vs. 0.97 ± 0.07; P < 0.001). A significant 29.50% ± 9.14% increase in oxidative stress was found in placentas of HIV-infected women (23.23 ± 1.64 vs. 17.94 ± 1.03; P < 0.01). A trend toward 41.18% ± 29.41% increased apoptosis active caspase-3/β-actin was found in HIV patients (0.48 ± 0.10 vs. 0.34 ± 0.05; P = not significant), confirmed by transferase dUTP nick end labeling assay. Adverse perinatal outcome did not correlate mitochondrial, oxidative, or apoptotic findings.
  
  
  
  Placentas of HIV-infected pregnant women under AZT cART showed evidence of mtDNA depletion, increased oxidative stress levels, and apoptosis suggestive of secondary mitochondrial failure, potential base of associated adverse perinatal outcome. Despite the fact that further demonstration of causality would need new approaches and bigger sample sizes, AZT-sparing cART should be considered in the context of pregnancy.
authors.affiliation: *Department of Maternal-Fetal Medicine, BCNatal-Hospital Clínic, University of Barcelona, Spain and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER); †Muscle Research and Mitochondrial Function Laboratory, Cellex IDIBAPS, Faculty of Medicine and Health Sciences, University of Barcelona, Internal Medicine Service-Hospital Clínic of Barcelona and CIBERER, Barcelona, Spain; and ‡Unit of Assisted Reproduction, Clínica Eugin, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hernández
authors.forename: Marc
authors.initials: M
authors.lastname: Catalán-García
authors.forename: Constanza
authors.initials: C
authors.lastname: Morén
authors.forename: Laura
authors.initials: L
authors.lastname: García-Otero
authors.forename: Marta
authors.initials: M
authors.lastname: López
authors.forename: Mariona
authors.initials: M
authors.lastname: Guitart-Mampel
authors.forename: José
authors.initials: J
authors.lastname: Milisenda
authors.forename: Oriol
authors.initials: O
authors.lastname: Coll
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
authors.forename: Eduard
authors.initials: E
authors.lastname: Gratacós
authors.forename: Òscar
authors.initials: Ò
authors.lastname: Miró
authors.forename: Glòria
authors.initials: G
authors.lastname: Garrabou
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects*; D016022:Case-Control Studies; D000075202:Contraindications; D003430:Cross-Sectional Studies; D004272:DNA, Mitochondrial / Q000187:drug effects*; D005260:Female; D005312:Fetal Blood / Q000187:drug effects; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008431:Maternal-Fetal Exchange / Q000187:drug effects*; D018384:Oxidative Stress; D010920:Placenta / Q000187:drug effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000188:drug therapy*; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D013030:Spain / Q000453:epidemiology; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D015215:Zidovudine