Abstract
BackgroundObesity 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.ResultsOur 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.ConclusionThis 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.
Highlights
Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity
Inclusion criteria was being in an infertile relationship and exclusion criteria were documented inflammatory or infectious disease, primary hypogonadism (Klinefelters Syndrome, cryptorchidism or testicular injury), the consumption of immunosuppressive medication (e.g., nonsteroidal anti-inflammatory drugs (NSAID), corticosteroids or fish oil), supplements that may alter intestinal function or any male hormonal therapy (i.e. aromatase inhibitors, clomiphene citrate, human chorionic gonadotropin or testosterone)
In summary we believe that obesity and its associated poor diet causes an increase in intestinal permeability that allows bacteria to transmigrate from the intestinal lumen into the circulation, resulting in activation of an inflammatory response
Summary
Obesity is known to be associated with inflammation, oxidative stress and a resulting reduction in sperm DNA integrity. Obesity is 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. 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. Fertilisation (IVF) treatment, even after controlling for maternal weight [7, 8] This may be of particular importance as the proportion of overweight or obese males in reproductive age men in the developed world exceeds 50% and appears to be increasing over time [9]. The total effect of obesity on hormone levels, semen parameters and sperm DNA integrity, is variable suggesting multiple mechanisms may be in play [12]
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