title: Mitochondrial toxicity and caspase activation in HIV pregnant women.
abstract: To assess the impact of HIV-infection and highly active anti-retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV-infected and -treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mtDNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome (OR: 4.81 [1.14-20.16]; P < 0.05) and decreased mtDNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naïve participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase-3 activation increased 63.64 ± 45.45% in controls (P < 0.001) and 100.00 ± 47.37% in HIV-pregnancies (P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV-infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti-retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size.
authors: Maternal-Fetal Medicine Department, Clinical Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic of Barcelona, Barcelona, Spain.|Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Sandra
authors: S
authors: Hernandez
authors: Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Constanza
authors: C
authors: Moren
authors: Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Marc
authors: M
authors: Catalán-García
authors: Maternal-Fetal Medicine Department, Clinical Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Marta
authors: M
authors: Lopez
authors: Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Mariona
authors: M
authors: Guitart-Mampel
authors: Clinica Eugin, Barcelona, Spain.
authors: Oriol
authors: O
authors: Coll
authors: Maternal-Fetal Medicine Department, Clinical Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Laura
authors: L
authors: Garcia
authors: Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Jose
authors: J
authors: Milisenda
authors: Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Angela
authors: A
authors: Justamante
authors: Infectious Disease, Hospital Clinic of Barcelona, Barcelona, Spain.
authors: Josep Maria
authors: JM
authors: Gatell
authors: Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Francesc
authors: F
authors: Cardellach
authors: Maternal-Fetal Medicine Department, Clinical Institute of Gynecology, Obstetrics and Neonatology, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Eduard
authors: E
authors: Gratacos
authors: Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Òscar
authors: Ò
authors: Miro
authors: Muscle Research and Mitochondrial Function Laboratory, Cellex-IDIBAPS, Faculty of Medicine-University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors: Gloria
authors: G
authors: Garrabou
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000139:chemically induced*
chemical_list: D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D053148:Caspase 3
keywords: 
  HAART
  ; 
  HIV
  ; mitochondrial toxicity; perinatal outcome; pregnancy