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- Title
Maternal L‐carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking.
- Authors
Stangenberg, Stefanie; Nguyen, Long The; Chan, Yik Lung; Zaky, Amgad; Pollock, Carol A.; Chen, Hui; Saad, Sonia
- Abstract
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.
- Subjects
CARNITINE; WOMEN'S tobacco use; PREGNANT women; ANIMAL epigenetics; PASSIVE smoking; KIDNEY abnormalities; SUBGROUP analysis (Experimental design); DNA methylation; DNA methyltransferases
- Publication
Clinical & Experimental Pharmacology & Physiology, 2019, Vol 46, Issue 2, p183
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.13038