Effects of maternal cigarette smoke exposure on renal and other health outcomes in mice offspring

Al-Odat, Ibrahim

Effects of maternal cigarette smoke exposure on renal and other health outcomes in mice offspring

Al-Odat, Ibrahim

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Publication Type:: Thesis
Issue Date:: 2016

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Field	Value	Language
dc.contributor.author	Al-Odat, Ibrahim
dc.date.accessioned	2016-03-28T23:13:52Z
dc.date.available	2016-03-28T23:13:52Z
dc.date.issued	2016
dc.identifier.uri	http://hdl.handle.net/10453/43398
dc.description	University of Technology Sydney. Faculty of Science.	en_AU
dc.description.abstract	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.	en_AU
dc.format	Thesis (PhD)
dc.language.iso	en_AU	en_AU
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/43398/2/02whole.pdf
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	au.edu.uts.lib/ppc
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Kidney disease.	en
dc.subject	Maternal cigarette smoke exposure (SE).	en
dc.subject	Intrauterine growth retardation (IUGR).	en
dc.subject	Glial cell line-derived neurotrophic factor (GDNF).	en
dc.subject	Adulthood renal dysfunction.	en
dc.subject	Lipid and glucose metabolic disorders.	en
dc.title	Effects of maternal cigarette smoke exposure on renal and other health outcomes in mice offspring	en_AU
dc.type	Thesis	en_AU
utslib.copyright.status	open_access

Abstract:

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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