Stefanie Stangenberg1, Long The Nguyen1, Yik Lung Chan2, Amgad Zaky1, Carol A Pollock1, Hui Chen3, Sonia Saad1,3. 1. Renal Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia. 2. RCMB, Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia. 3. Faculty of Science, School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia.
Abstract
OBJECTIVES: Epidemiological and animal studies showed that L-carnitine (LC) supplementation can ameliorate oxidative stress-induced tissues damage. We have previously shown that maternal cigarette smoke exposure (SE) can increase renal oxidative stress in newborn offspring with postnatal kidney underdevelopment and renal dysfunction in adulthood, which were normalised by LC administration in the SE dams during pregnancy. Exposure to an adverse intrauterine environment may lead to alteration in the epigenome, a mechanism by which adverse prenatal conditions increase the susceptibility to chronic disease later in life. The current study aimed to determine whether maternal SE induces epigenetic changes in the offspring's kidney are associated with renal underdevelopment, and the protective effect of maternal LC supplementation. METHOD: Female Balb/c mice (7 weeks) were exposed to cigarette smoke (SE) or air (Sham) for 6 weeks prior to mating, during gestation and lactation. A subgroup of the SE dams received LC via drinking water (SE + LC, 1.5 mmol/L) throughout gestation and lactation. Male offspring were studied at postnatal day (P)1, P20, and 13 weeks. RESULTS: Maternal SE altered the expression of renal development markers glial cell line-derived neurotrophic factor and fibroblast growth factor 2, which were associated with increased renal global DNA methylation and DNA methyltransferase 1 mRNA expression at birth. These disorders were reversed by maternal LC administration. CONCLUSION: The effect of maternal SE on renal underdevelopment involves global epigenetic alterations from birth, which can be prevented by maternal LC supplementation.
OBJECTIVES: Epidemiological and animal studies showed that L-carnitine (LC) supplementation can ameliorate oxidative stress-induced tissues damage. We have previously shown that maternal cigarette smoke exposure (SE) can increase renal oxidative stress in newborn offspring with postnatal kidney underdevelopment and renal dysfunction in adulthood, which were normalised by LC administration in the SE dams during pregnancy. Exposure to an adverse intrauterine environment may lead to alteration in the epigenome, a mechanism by which adverse prenatal conditions increase the susceptibility to chronic disease later in life. The current study aimed to determine whether maternal SE induces epigenetic changes in the offspring's kidney are associated with renal underdevelopment, and the protective effect of maternal LC supplementation. METHOD: Female Balb/c mice (7 weeks) were exposed to cigarette smoke (SE) or air (Sham) for 6 weeks prior to mating, during gestation and lactation. A subgroup of the SE dams received LC via drinking water (SE + LC, 1.5 mmol/L) throughout gestation and lactation. Male offspring were studied at postnatal day (P)1, P20, and 13 weeks. RESULTS: Maternal SE altered the expression of renal development markers glial cell line-derived neurotrophic factor and fibroblast growth factor 2, which were associated with increased renal global DNA methylation and DNA methyltransferase 1 mRNA expression at birth. These disorders were reversed by maternal LC administration. CONCLUSION: The effect of maternal SE on renal underdevelopment involves global epigenetic alterations from birth, which can be prevented by maternal LC supplementation.
Authors: Hui Chen; Brian G Oliver; Anushriya Pant; Annabel Olivera; Philip Poronnik; Carol A Pollock; Sonia Saad Journal: Antioxidants (Basel) Date: 2021-05-06
Authors: Baoming Wang; Yik-Lung Chan; Gerard Li; Kin Fai Ho; Ayad G Anwer; Bradford J Smith; Hai Guo; Bin Jalaludin; Cristan Herbert; Paul S Thomas; Jiayan Liao; David G Chapman; Paul S Foster; Sonia Saad; Hui Chen; Brian G Oliver Journal: Antioxidants (Basel) Date: 2021-06-25