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

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Pearce, Karma L
Hill, Amy
Tremellen, Kelton P
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© The Author(s). 2019
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The Author(s).
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.
© The Author(s). 2019 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Metabolic endotoxemia, LPS, Sperm DNA integrity, Intestinal permeability, Oxidative stress
Pearce, K. L., Hill, A., & Tremellen, K. P. (2019). Obesity related metabolic endotoxemia is associated with oxidative stress and impaired sperm DNA integrity. Basic and Clinical Andrology, 29(1). https://doi.org/10.1186/s12610-019-0087-5