MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS AND FETAL PROGRAMMING OF KIDNEY DISEASE INDUCED BY MATERNAL SMOKING — The Association Specialists
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MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS AND FETAL PROGRAMMING OF KIDNEY DISEASE INDUCED BY MATERNAL SMOKING (410)

Stefanie Stangenberg 1 , Long T Nguyen 2 , Ibrahim Al-Odat 2 , Hui Chen 2 , Murray Killingsworth 3 , Carol A Pollock 1 , Sonia Saad 1
  1. Kolling Institute of Medical Research, Sydney/St Leonards, NSW, Australia
  2. School of Medical and Molecular Biosciences, University of Technology, Sydney, NSW, Australia
  3. Department of Anatomical Pathology, University of New South Wales, Sydney, NSW, Australia

Aim: To determine the effect of maternal smoking on mitochondrial function, oxidative stress and susceptibility to kidney disease in the offspring

Background: The role of an adverse in-utero environment on programming of chronic adulthood diseases is emerging. Maternal smoking during gestation is associated with increased levels of oxidative stress in mothers, newborns and infants, which is also linked to low birth weight. The association between low birth weight and chronic kidney disease has been well described; however the mechanisms underlying such susceptibility later in life remain unknown.

Methods: Female Balb/c mice were sham or cigarette smoke exposed (SE) generated from 2 cigarettes twice daily for 6 weeks before mating, throughout gestation and lactation. Male offspring were sacrificed at day 1, day 20 (weaning) and week 13 (mature age). Blood and urine were collected and kidneys were harvested to determine mitochondrial function and oxidative stress. MnSOD, OXPHOS Complexes (COX I-V) and TOM20 were determined by Western blot. Mitochondrial copy number was determined by real-time PCR. Oxidative stress was assessed by 8-OHdG immunostaining and CellROX™. Mitochondrial and renal structures were examined using electron microscopy and histology.

Results: Offspring from SE mothers had low birth weight and impaired glucose tolerance at 13 weeks. Renal cytosolic and mitochondrial MnSOD were significantly reduced in offspring of SE mothers and Cell ROX and 8-OHdG were increased in the SE offspring. Mitochondrial outer membrane protein TOM20 and COX I-V were significantly reduced in the SE offspring in the face of mitochondrial structural change and alteration in mitochondrial DNA copy number. Although there was no difference in serum creatinine level, urine albumin/creatinine ratio was significantly increased in the SE offspring at adulthood.

Conclusions: Maternal smoking increased renal oxidative stress and mitochondrial dysfunction in offspring early in life, resulting in predisposition to renal dysfunction in adulthood.