Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity

Abstract Background Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity. Importantly, obesity is also reported to be associated with an increase in intestinal permeability with the passage of intestinal bacteria into the circulation...

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Main Authors: Karma L. Pearce, Amy Hill, Kelton P. Tremellen
Format: Article
Language:English
Published: BMC 2019-05-01
Series:Basic and Clinical Andrology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12610-019-0087-5
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author Karma L. Pearce
Amy Hill
Kelton P. Tremellen
author_facet Karma L. Pearce
Amy Hill
Kelton P. Tremellen
author_sort Karma L. Pearce
collection DOAJ
description Abstract Background Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity. Importantly, obesity is also reported to be associated with an increase in intestinal permeability with the passage of intestinal bacteria into the circulation (metabolic endotoxemia) that triggers a systemic state of inflammation and resultant oxidative stress. Therefore, we hypothesised that this obesity related increase in intestinal permeability and resultant metabolic endotoxemia (ME) may activate inflammation within the male reproductive tract, leading to increased reactive oxygen species production, sperm oxidative stress and a decline in DNA integrity. Results Our pilot study of 37 infertile men confirmed a significant positive correlation between body mass index (BMI), increased intestinal permeability (serum zonulin), metabolic endotoxaemia (LBP), sperm DNA oxidative damage (seminal 8 OhDG) and increasing levels of sperm DNA fragmentation (Halosperm). Metabolic endotoxemia was positively correlated with increasing levels of sperm DNA oxidative damage with this relationship remaining significant, even after adjustment for relevant confounders such as age, BMI and days of abstinence. These observations suggest that metabolic endotoxemia and its associated oxidative stress may be a key driver of sperm DNA damage in obese men. Conclusion This study confirms a link between obesity, increasing intestinal permeability and endotoxin exposure, and oxidative mediated sperm DNA damage. This warrants further investigation to fully understand the effect of metabolic endotoxemia on male reproductive function which could result in the new therapies to improve male fertility potential.
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spelling doaj.art-5d8044ac57da44219d441a8ad12c6cc22022-12-22T01:58:56ZengBMCBasic and Clinical Andrology2051-41902019-05-012911910.1186/s12610-019-0087-5Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrityKarma L. Pearce0Amy Hill1Kelton P. Tremellen2School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South AustraliaSchool of Pharmacy and Medical Sciences, Division of Health Sciences, University of South AustraliaSchool of Pharmacy and Medical Sciences, Division of Health Sciences, University of South AustraliaAbstract Background Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity. Importantly, obesity is also reported to be associated with an increase in intestinal permeability with the passage of intestinal bacteria into the circulation (metabolic endotoxemia) that triggers a systemic state of inflammation and resultant oxidative stress. Therefore, we hypothesised that this obesity related increase in intestinal permeability and resultant metabolic endotoxemia (ME) may activate inflammation within the male reproductive tract, leading to increased reactive oxygen species production, sperm oxidative stress and a decline in DNA integrity. Results Our pilot study of 37 infertile men confirmed a significant positive correlation between body mass index (BMI), increased intestinal permeability (serum zonulin), metabolic endotoxaemia (LBP), sperm DNA oxidative damage (seminal 8 OhDG) and increasing levels of sperm DNA fragmentation (Halosperm). Metabolic endotoxemia was positively correlated with increasing levels of sperm DNA oxidative damage with this relationship remaining significant, even after adjustment for relevant confounders such as age, BMI and days of abstinence. These observations suggest that metabolic endotoxemia and its associated oxidative stress may be a key driver of sperm DNA damage in obese men. Conclusion This study confirms a link between obesity, increasing intestinal permeability and endotoxin exposure, and oxidative mediated sperm DNA damage. This warrants further investigation to fully understand the effect of metabolic endotoxemia on male reproductive function which could result in the new therapies to improve male fertility potential.http://link.springer.com/article/10.1186/s12610-019-0087-5Metabolic endotoxemiaLPSSperm DNA integrityIntestinal permeabilityOxidative stress
spellingShingle Karma L. Pearce
Amy Hill
Kelton P. Tremellen
Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity
Basic and Clinical Andrology
Metabolic endotoxemia
LPS
Sperm DNA integrity
Intestinal permeability
Oxidative stress
title Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity
title_full Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity
title_fullStr Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity
title_full_unstemmed Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity
title_short Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity
title_sort obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm dna integrity
topic Metabolic endotoxemia
LPS
Sperm DNA integrity
Intestinal permeability
Oxidative stress
url http://link.springer.com/article/10.1186/s12610-019-0087-5
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AT amyhill obesityrelatedmetabolicendotoxemiaisassociatedwithoxidativestressandimpairedspermdnaintegrity
AT keltonptremellen obesityrelatedmetabolicendotoxemiaisassociatedwithoxidativestressandimpairedspermdnaintegrity