Sperm DNA oxidative damage and DNA adducts

Abstract

The objective of this study was to investigate DNA damage and adducts in sperm from coke oven workers who have been exposed to polycyclic aromatic hydrocarbons. A longitudinal study was conducted with repeated measurements during spermatogenesis. Coke-oven workers (n=112) from a coke-oven plant served the PAH-exposed group, while administrators and security personnel (n=67) served the control. Routine semen parameters (concentration, motility, vitality, and morphology) were analyzed simultaneously; the assessment of sperm DNA integrity endpoints included DNA fragmentation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGuo). The degree of sperm DNA fragmentation was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and sperm chromatin structure assay (SCSA). The PAH-exposed group had a significant increase in bulky DNA adducts and 8-oxo-dGuo compared to the control subjects (Ps = 0.002 and 0.045, respectively). Coke oven workers' percentages of DNA fragmentation and denaturation from the PAH-exposed group were not significantly different from those of the control subjects (Ps = 0.232 and 0.245, respectively). Routine semen parameters and DNA integrity endpoints were not correlated. Concentrations of 8-oxo-dGuo were positively correlated with percentages of DNA fragmentation measured by both TUNEL and SCSA (Ps = 0.045 and 0.034, respectively). However, the concentrations of 8-oxo-dGuo and percentages of DNA fragmentation did not correlate with concentrations of bulky DNA adducts. In summary, coke oven workers with chronic exposure to PAHs experienced decreased sperm DNA integrity. Oxidative stress could contribute to the degree of DNA fragmentation. Bulky DNA adducts may be independent of the formation of DNA fragmentation and oxidative adducts in sperm. Monitoring sperm DNA integrity is recommended as a part of the process of assessing the impact of occupational and environmental toxins on sperm.

Acrosome reaction and chromatin integrity as additional parameters of semen analysis to predict fertilization and blastocyst rates

“…DNA fragmentation of germ cells can occur as a result of apoptosis, by chromatin compaction during the replacement of histones by protamines [ 33 ], by oxidative stress mechanisms derived from lifestyle or exposure to xenobiotics like pesticides, among others, which are considered risk factors of poor semen quality [ 13 , 31 , 39 ]. Oxidative stress, mainly in the epididymis and during transport in the seminal fluid, is the main responsible for the DNA damage caused by the generation of oxidized bases as 8-hydroxy,2′ deoxyguanosine (8-OHdG), and the subsequent strand breaks due to the lack of repair mechanisms [ 14 , 76 ]. In addition, exposure to radiation or toxic agents induces DNA damage, which stimulates the synthesis of p53 proteins that are cell sensors activating pro-apoptotic proteins to trigger apoptosis [ 77 ].…”

“…Due that semen quality assessed by WHO criteria does not fully predict male fertility [ 8 ], new methodologies have been developed to determine sperm quality and function, including proteomic analysis [ 9 , 10 ], apoptotic markers [ 11 ], oxidative status [ 12 , 13 ], DNA adducts [ 14 ], and DNA methylation status [ 15 ], obtaining good associations with male fertility. Unfortunately, these techniques are expensive and difficult to include in the operational process in andrology laboratories, and therefore have not had continuity.…”

Nitric oxide, 8-hydroxydeoxyguanosine, and total antioxidant capacity in human seminal plasma of infertile men and their relationship with sperm parameters

“…Leukocytes and immature, or abnormal spermatozoa are the major endogenous sources of ROS in the seminal plasma [3,4]. Although limited levels of ROS are necessary for the processes of spermatozoa maturation, capacitation, hy-peractivation, acrosome reaction, and sperm-oocyte fusion, increased content of ROS can attack sperm DNA, lipids and proteins, which is subsequently associated with cell death, poor quality of sperm, and male infertility [4,5]. The excessive levels of ROS are commonly overwhelmed by the body' s antioxidant defense mechanisms; total antioxidant capacity (TAC) that contains both enzymatic and non-enzymatic antioxidant molecules such as superoxide dismutase (SOD), catalase, glutathione peroxidase, ascorbate, vitamin E, pyruvate, glutathione.…”

“…The excessive levels of ROS are commonly overwhelmed by the body' s antioxidant defense mechanisms; total antioxidant capacity (TAC) that contains both enzymatic and non-enzymatic antioxidant molecules such as superoxide dismutase (SOD), catalase, glutathione peroxidase, ascorbate, vitamin E, pyruvate, glutathione. However, spermatozoa are unable to restore the oxidative damage due to (1) the high content of polyunsaturated fatty acids in their cell membrane which makes them highly susceptible to ROS by inducing lipid peroxidation, (2) the partial loss of antioxidant protection due to the limit volume of cytoplasm, (3) their lack of the necessary cytoplasmic enzyme repair systems [1][2][3][4][5].…”

Environmental PAH exposure and male idiopathic infertility: a review on early life exposures and adult diagnosis

“…Men who smoke, or are exposed to PAHs through occupation, have bulky PAH-DNA adducts in sperm, reduced sperm count and motility and alterations in morphology [15, 16]. Semen is used a biomarker of environmental pollutant exposure, including that of PAHs [9, 17, 18].…”