Effects of maternal cigarette smoke exposure on renal and other health outcomes in mice offspring
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Background: The burden of kidney disease is significantly increased worldwide. Developmental programming of non-communicable diseases is an established paradigm. Therefore, there is increasing attention to the contribution of intrauterine and early post-natal environmental insults to the risk of adulthood kidney diseases. One of such insults is maternal cigarette smoke exposure (SE), which is associated with intrauterine growth retardation (IUGR) and some adulthood diseases in offspring. However, it is unknown whether maternal SE can increase the risk of developing chronic kidney disease (CKD) in offspring. Maternal SE was also shown to increase renal oxidative stress in offspring; while the anti-oxidants L-carnitine (LC) supplementation has been shown to be beneficial in many human diseases, which may benefit such offspring. Objectives: This thesis aimed to study the effect of maternal SE on, 1) kidney development and renal function; 2) glucose and lipid metabolic markers in the liver, and; 3) the effect of maternal LC supplementation during gestation and lactation on health outcome of the SE offspring. Methods: Female Balb/c breeder mice were exposed to cigarette smoke for 6 weeks prior to mating, during gestation and lactation; with sham exposure as control. A subgroup of the SE dams was treated with LC (SE+L-C) during gestation and lactation via drinking water. The offspring were sacrificed at postnatal day (P)1, P20 (weaning age) and 13 weeks (mature age). Blood, urine, kidneys and livers were collected. Renal Morphology and function, renal development factors, and metabolic markers in the liver were examined in the offspring. Results: Reduced nephrons number, enlarged glomerular size and altered renal expression of developmental factors such as glial cell line-derived neurotrophic factor (GDNF) and paired box binding protein (Pax)2 were observed in the offspring. This was linked to increased mRNA expression of pro-inflammatory marker, monocyte chemoattractant protein (MCP)-1, and urine albumin/creatinine ratio at adulthood in the male offspring. However female offspring were protected from such maternal effect. Both genders developed glucose intolerance. mRNA expression of IL-1β and TNF-α was upregulated in the liver in the female offspring, with hyperlipidemia. Maternal LC supplementation during gestation and lactation ameliorated these changes in the offspring by maternal SE. Conclusion: Maternal SE led to kidney underdevelopment, adulthood renal dysfunction, lipid and glucose metabolic disorders, and increased renal and liver inflammation in the offspring in a gender-specific manner. Maternal LC supplementation has a beneficial role in ameliorating the detrimental impact of maternal SE on the offspring.
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