Maternal smoking induces mitochondrial dysfunction and oxidative stress in offspring kidneys

Aim: To determine the effect of maternal smoking on oxidative stress, mitochondrial function and susceptibility to chronic 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 low birth weight and increased oxidative stress in mothers and newborns. The association between low birth weight and chronic kidney disease in later life is well described, however the mechanisms underlying such susceptibility remain unknown. Methods: Female Balb/c mice were sham or cigarette smoke exposed (SE) 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 was collected, kidneys were harvested to determine mitochondrial function and oxidative stress. Mitochondrial superoxide dismutase (MnSOD), oxidative phosphorylation (OXPHOS) complexes I-V and mitochondrial outer membrane protein (TOM20) were determined. Oxidative stress was assessed by CellROX™ and localised by Mitotracker® co-stain. Mitochondria were examined by electron microscopy. Mitochondrial copy number was determined by real-time PCR. Results: Offspring from SE mothers had low birth weight and increased albumin/ creatinine ratio at adulthood. Renal oxidative stress was increased in mitochondria of SE offspring. OXPHOS enzymes, TOM20 as well as MnSOD level and activity were significantly reduced at day 1 and week 13. Mitochondria were enlarged and reduced in number at week 13, although mitochondrial DNA copy number did not change. Conclusions: Maternal smoking leads to oxidative stress, mitochondrial dysfunction and adult onset albuminuria in the offspring kidney. The mitochondrial dysfunction and reduced antioxidant capacity may predispose to further renal damage in the setting of other insults.