Maternal L‐carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking

• Published in: Clinical and experimental pharmacology & physiology 2019-02, Vol.46 (2), p.183-193
• Main Authors: Stangenberg, Stefanie, Nguyen, Long The, Chan, Yik Lung, Zaky, Amgad, Pollock, Carol A., Chen, Hui, Saad, Sonia
• Format: Article
• Language: English
• Subjects: Animals; antioxidant; Breastfeeding & lactation; Carnitine; Carnitine - pharmacology; Cell Proliferation - drug effects; Chronic illnesses; Cigarette smoke; Deoxyribonucleic acid; Dietary Supplements; DNA; DNA methylation; DNA methyltransferase; Drinking water; Epidemiology; Epigenesis, Genetic - drug effects; Epigenetics; Exposure; Female; Fibroblast growth factor 2; Fibroblasts - drug effects; Fibroblasts - pathology; Gene expression; Gestation; Glial Cell Line-Derived Neurotrophic Factor - metabolism; Glial cells; global methylation; Growth factors; Intrauterine exposure; Kidney - drug effects; Kidney - growth & development; Kidney - metabolism; Kidney - pathology; kidney development; Kidneys; Lactation; Male; Maternal Exposure - adverse effects; maternal smoking; Methylation - drug effects; Mice; Mice, Inbred BALB C; Neuronal-glial interactions; Neurotrophic factors; Offspring; Oxidative stress; Oxidative Stress - drug effects; Pregnancy; Prenatal Exposure Delayed Effects - genetics; Prenatal Exposure Delayed Effects - pathology; Prenatal Exposure Delayed Effects - physiopathology; Prenatal Exposure Delayed Effects - prevention & control; Renal function; Signal Transduction - drug effects; Smoke; Smoking; Smoking - adverse effects; Subgroups; Supplements
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13038

Summary 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.