title: Molecular basis of reduced birth weight in smoking pregnant women: mitochondrial dysfunction and apoptosis.
abstract: In utero exposure of fetuses to tobacco is associated with reduced birth weight. We hypothesized that this may be due to the toxic effect of carbon monoxide (CO) from tobacco, which has previously been described to damage mitochondria in non-pregnant adult smokers. Maternal peripheral blood mononuclear cells (PBMCs), newborn cord blood mononuclear cells (CBMCs) and placenta were collected from 30 smoking pregnant women and their newborns and classified as moderate and severe smoking groups, and compared to a cohort of 21 non-smoking controls. A biomarker for tobacco consumption (cotinine) was assessed by ELISA (enzyme-linked immunosorbent assay). The following parameters were measured in all tissues: mitochondrial chain complex IV [cytochrome c oxidase (COX)] activity by spectrophotometry, mitochondrial DNA levels by reverse transcription polymerase chain reaction, oxidative stress by spectrophotometric lipid peroxide quantification, mitochondrial mass through citrate synthase spectrophotometric activity and apoptosis by Western blot parallelly confirmed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assay in placenta. Newborns from smoking pregnant women presented reduced birth weight by 10.75 percent. Materno-fetal mitochondrial and apoptotic PBMC and CBMC parameters showed altered and correlated values regarding COX activity, mitochondrial DNA, oxidative stress and apoptosis. Placenta partially compensated this dysfunction by increasing mitochondrial number; even so ratios of oxidative stress and apoptosis were increased. A CO-induced mitotoxic and apoptotic fingerprint is present in smoking pregnant women and their newborn, with a lack of filtering effect from the placenta. Tobacco consumption correlated with a reduction in birth weight and mitochondrial and apoptotic impairment, suggesting that both could be the cause of the reduced birth weight in smoking pregnant women.
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX- IDIBAPS, Faculty of Medicine-University of Barcelona, Internal Medicine Department-Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Glòria
authors.initials: G
authors.lastname: Garrabou
authors.affiliation: Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.|Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Ana-Sandra
authors.initials: AS
authors.lastname: Hernàndez
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX- IDIBAPS, Faculty of Medicine-University of Barcelona, Internal Medicine Department-Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Catalán García
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX- IDIBAPS, Faculty of Medicine-University of Barcelona, Internal Medicine Department-Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Constanza
authors.initials: C
authors.lastname: Morén
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX- IDIBAPS, Faculty of Medicine-University of Barcelona, Internal Medicine Department-Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Tobías
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX- IDIBAPS, Faculty of Medicine-University of Barcelona, Internal Medicine Department-Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Sarai
authors.initials: S
authors.lastname: Córdoba
authors.affiliation: Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.|Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: López
authors.affiliation: Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.|Department of Maternal-Fetal Medicine, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Figueras
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX- IDIBAPS, Faculty of Medicine-University of Barcelona, Internal Medicine Department-Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grau
authors.affiliation: Muscle Research and Mitochondrial Function Laboratory, CELLEX- IDIBAPS, Faculty of Medicine-University of Barcelona, Internal Medicine Department-Hospital Clinic of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Valencia, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
mesh_terms: D000328:Adult; D017209:Apoptosis; D001724:Birth Weight / Q000502:physiology*; D015153:Blotting, Western; D002248:Carbon Monoxide; D016022:Case-Control Studies; D003367:Cotinine / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000378:metabolism*; D013053:Spectrophotometry
chemical_list: D004272:DNA, Mitochondrial; D008054:Lipid Peroxides; D002248:Carbon Monoxide; D003576:Electron Transport Complex IV; D003367:Cotinine
keywords: Carbon monoxide (CO); intrauterine growth restriction (IGR); pregnancy; tobacco