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

Abstract

Obesity prevalence worldwide is increasing significantly. Whilst maternal obesity has clear detrimental impacts on fertility, pregnancy and foetal 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 affects basic sperm parameters such as sperm count, concentration and motility, increases the incidence of 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. Whilst, there are still conflicting data in humans as to the association of obesity in men with sperm DNA damage, evidence from rodent models is clear, indicating that male obesity increases sperm DNA damage. Human data are often conflicting because of 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. Furthermore, comorbidities 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 that is 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 and 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 resulting from obesity. Finally, we summarise intergenerational obesity through the paternal linage and how sperm DNA damage may contribute to the transmission.

The influence of lifestyle and biological factors on semen variability

“…The low sample number ( N = 118 samples from 29 men) also likely contributed to the weak to moderate strength associations between biological and lifestyle factors and measures of both basic and extended semen parameters, with some correlations going in the opposite direction to that expected. For instance, BMI was weakly negatively associated with sperm DNA damage and lipid peroxidation a direct opposite to that of the current literature [ 32 ]. Whilst other relationships correlated as expected, such as sperm DNA damage and lipid peroxidation both positively correlating with abstinence, a factor which is known to increase sperm oxidative stress [ 38 ].…”

“…We observed only weak to moderate associations likely due to our low sample size (a limitation of our pilot trial), which were consistent with those previously reported in the literature. For instance, we found negative associations between traditional sperm parameters of count, motility, and morphology with age [ 30 ], BMI [ 31 , 32 ], waist circumference [ 33 , 34 ], and general health and psychological wellbeing [ 35 ]. Dietary intake, which displayed the biggest variations across collections in our cohort, was also associated with semen quality.…”

Association between adverse nutrition status by BMI and increased time-to-pregnancy in planed pregnancy couples: A cohort study in Guangzhou, China

“…In males, a meta-analysis suggests a signi cant correlation between increased BMI and decreased seminal volume, sperm count, concentration, and viability [34]. Additionally, in animal studies, obesity is correlated with increased sperm DNA damage, but ndings in human studies are inconsistent in this regard [35]. The abnormal lipid pro le in obese males may lead to testicular oxidative stress, which is a common pathway for disruption in sperm function [36].…”

Sperm DNA integrity: a special issue exploring the causes, consequences, and treatment of DNA damage in human spermatozoa

“…One of many potential causes of oxidative stress with the male reproductive system is the global pandemic in obesity. In this Special Issue, Peel et al 20 summarized the latest animal and human data suggesting that obesity is associated with an increase in sperm DNA damage via a range of direct and indirect mechanisms. These authors highlight the potential role of oxidative stress in not only mediating the impact of obesity on sperm DNA damage, but also in the transgenerational inheritance of obesity.…”

“…One of many potential causes of oxidative stress with the male reproductive system is the global pandemic in obesity. In this Special Issue, Peel et al 20 . summarized the latest animal and human data suggesting that obesity is associated with an increase in sperm DNA damage via a range of direct and indirect mechanisms.…”