Sperm DNA damage: the possible link between obesity and male infertility, an update of the current literature.

Obesity prevalence worldwide is increasing significantly. Whilst maternal obesity has clear detrimental impacts on fertility, pregnancy and fetal outcomes, more recently there has been an increasing focus on the role of paternal obesity in human fertility. Recent meta-analyses have indicated that obesity in men negatively effects basic sperm parameters such as sperm count, concentration and motility, increases the incidents of being diagnosed with infertility and reduces the chances of conception. Sperm DNA damage, typically characterised by DNA strand breaks and oxidation of DNA nucleotides, is a specialised marker of sperm quality that has been independently associated with recurrent miscarriage, reduced assisted reproduction success and increased mutational loads in subsequent offspring. While, there is still conflicting data in humans as to the association of obesity in men with sperm DNA damage, evident from rodent models are clear, indicating that male obesity increases sperm DNA damage. Human data is often conflicted due to the large heterogeneity amongst studies, the use of body mass index as the indicator of obesity and the methods used for detection of sperm DNA damage. Further, co-morbidities of obesity (i.e. heat stress, adipokines, insulin resistance, changes in lipids, hypogonadism and obstructive sleep apnoea) are also independently associated with increased sperm DNA damage are not always modified in men with obesity, and as such may provide a causative link to the discrepancies amongst human studies. In this review, we provide an update on the literature regarding the associations between obesity in men on fertility, basic sperm parameters and sperm DNA damage. We further discuss potential reasons for the discrepancies in the literature and outline possible direct and indirect mechanisms of increased sperm DNA damage resultant from obesity. Finally, we summarise intergenerational obesity through the paternal linage and how sperm DNA damage may contribute to the transmission. This article is protected by copyright. All rights reserved.