Sperm DNA integrity is essential for the accurate transmission of genetic information. It has a highly compact and complex structure and is capable of decondensation-features that must be present in order for a spermatozoon to be considered fertile. Any form of sperm chromatin abnormalities or DNA damage may result in male infertility. In support of this conclusion, it was reported that in-vivo fecundity decreases progressively when > 30% of the spermatozoa are identified as having DNA damage. Several methods are used to assess sperm chromatin/DNA, which is considered an independent measure of sperm quality that may yield better diagnostic and prognostic approaches than standard sperm parameters (concentration, motility and morphology). The clinical significance of this assessment lies in its association not only with natural conception rates, but also with assisted reproduction success rates. Also, it has a serious impact on the offspring and is highly prognostic in the assessment of fertility in cancer patients. Therefore, screening for sperm DNA damage may provide useful information in cases of male idiopathic infertility and in those men pursuing assisted reproduction. Treatment should include methods for prevention of sperm DNA damage.

/pdf/role-of-sperm-chromatin-abnormalities-and-dna-damage-in-male-5a2riixlg7.pdf

Role of sperm chromatin abnormalities and DNA damage in male infertility

Spermatozoa are highly vulnerable to oxidative attack because they lack significant antioxidant protection due to the limited volume and restricted distribution of cytoplasmic space in which to house an appropriate armoury of defensive enzymes. In particular, sperm membrane lipids are susceptible to oxidative stress because they abound in significant amounts of polyunsaturated fatty acids. Susceptibility to oxidative attack is further exacerbated by the fact that these cells actively generate reactive oxygen species (ROS) in order to drive the increase in tyrosine phosphorylation associated with sperm capacitation. However, this positive role for ROS is reversed when spermatozoa are stressed. Under these conditions, they default to an intrinsic apoptotic pathway characterised by mitochondrial ROS generation, loss of mitochondrial membrane potential, caspase activation, phosphatidylserine exposure and oxidative DNA damage. In responding to oxidative stress, spermatozoa only possess the first enzyme in the base excision repair pathway, 8-oxoguanine DNA glycosylase. This enzyme catalyses the formation of abasic sites, thereby destabilising the DNA backbone and generating strand breaks. Because oxidative damage to sperm DNA is associated with both miscarriage and developmental abnormalities in the offspring, strategies for the amelioration of such stress, including the development of effective antioxidant formulations, are becoming increasingly urgent.

Causes and consequences of oxidative stress in spermatozoa.

The impact of sexually transmitted diseases (STD) on male fertility is strongly dependent on the local prevalence of the STDs. In Western countries STD-infections are of minor relevance. In other regions, i.e. Africa or South East Asia, the situation appears to be different. Acute urethritis could not be associated with male infertility. Chronic infections (gonorrhoea) can cause urethral strictures and epididymo-orchitis. Chlamydia trachomatis and Neisseria gonorrhoea can be transmitted to the female partner and cause pelvic inflammatory disease with tubal obstruction. Ureaplasma urealyticum may impair spermatozoa (motility, DNA condensation). Trichomonas vaginalis has, if any, only minor influence on male fertility. The relevance of viral infections (HPV, HSV) for male infertility is not resolved. Any STD increases the chances of transmission of the human immunodeficiency virus (HIV). The HIV infection is associated with infectious semen and the risk of virus transmission. Semen quality deteriorates with the progression of immunodeficiency. Special counselling of serodiscordant couples is needed. STDs should be treated early and adequately to prevent late sequelae for both men and women.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1439-0272.2007.00825.x

Sexually transmitted infections: Impact on male fertility

Oxidative stress (OS), defined as an overabundance of reactive oxygen species (ROS) or a deficiency of antioxidants, has been linked to sperm damage and male infertility. There are many sources of OS and inflammation including varicocele, tobacco usage, alcohol, obesity/metabolic syndrome, leukocytospermia, sexually transmitted disease (i.e., Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum), bacterial prostatitis, microorganism mutations leading to more OS, and viral infections (i.e., human immunodeficiency virus, hepatitis). This review is focusing on infection and inflammation-mediated OS, the inflammatory markers underlying pathology, clinical significance in male infertility, and a brief description of the recommended treatment modalities.

Role of oxidative stress, infection and inflammation in male infertility.

Background
Genital ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) and mycoplasmas (Mycoplasma genitalium and Mycoplasma hominis) are potentially pathogenic species playing an etiologic role in both genital infections and male infertility. Reports are, however, controversial regarding the effects of these microorganisms infections in the sperm seminological variables. This study aimed at determining the frequency of genital ureplasmas and mycoplasmas in semen specimens collected from infertile men, and at comparing the seminological variables of semen from infected and non-infected men with these microorganisms.

/pdf/ureaplasma-urealyticum-ureaplasma-parvum-mycoplasma-hominis-ges9n6vhna.pdf

Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis and Mycoplasma genitalium infections and semen quality of infertile men

The incidence of Ureaplasma urealyticum infection in the semen of infertile men is variable (7%–42%). Evidence has accumulated through routine semen analysis to suggest that this infection can cause embryo loss without necessarily affecting sperm quality. The aim of this study was to specifically investigate the effects of U. urealyticum infection on sperm chromatin stability and DNA integrity, which are known to be correlated to pregnancy outcome. Sperm cells isolated from human semen infected in vivo with U. urealyticum exhibited a low percentage of stable chromatin as determined by nuclear chromatin decondensation assay (42% ± 4.8%, n = 8) and a high percent of denatured DNA as determined by sperm chromatin structure assay (60.9% ± 9.1%, n = 7). After doxycyclin treatment, a significant improvement in both parameters was observed (73.7% ± 3.6%, P < 0.001 and 30.1% ± 3.5%, P < 0.008, respectively). Sperm cells infected in vitro exhibited higher rates of viability and motility than uninfected ce...

https://bioone.org/journals/Biology-of-Reproduction/volume-63/issue-4/biolreprod63.4.1041/In-Vivo-and-In-Vitro-Impairment-of-Human-and-Ram/10.1095/biolreprod63.4.1041.pdf

In Vivo and In Vitro Impairment of Human and Ram Sperm Nuclear Chromatin Integrity by Sexually Transmitted Ureaplasma urealyticum Infection

Genital Ureaplasma urealyticum infection is consid- ered a sexually transmitted infection. It has long been debated whether the presence of U urealyticum in semen may be a possible cause of infertility. Long-term incubation (4 hours or overnight) of sperm cells with U urealyticum in vitro resulted in a significant in- hibition of sperm motility and membrane alteration whereas a short incubation (45 minutes) of sperm cells with ureaplasmas resulted in an acceleration of sperm velocity. The aim of this study was to understand these contradictory reports of U urealyticum infection on sperm motility. Spermatozoa from fresh ejaculates of normozoospermic semen of men who were referred to the univer- sity Male Fertility Laboratory for semen analysis, with no history of genital tract infection, and from normal Assaf breed rams were infected in vitro with U urealyticum serotype 8, at different pHs and O2 concentrations. Sperm viability and motility and changes in ex- tracellular pH were evaluated. A significant (16%-43%) increase in sperm activity was observed upon infection at alkaline pH (7.8) under aerobic or hypoxic conditions, and a 58% increase was ob- served under anaerobic conditions and pH 7.2. When the infection was conducted under aerobic conditions and acidic pH (6.3), or under hypoxic conditions at neutral pH (7.2), an 8%-25% inhibition of sperm activity was observed. These results indicate that when sperm activity depends on mitochondrial oxidative phosphoryla- tion, usually at low pHs, U urealyticum competes with mitochon- drial energy production and therefore reduces sperm motility and viability. However, when sperm energy metabolism depends on glycolysis, usually at higher pHs, U urealyticum stimulates glycol- ysis and sperm activity.

Malka Reichart

Papers

In Vivo and In Vitro Impairment of Human and Ram Sperm Nuclear Chromatin Integrity by Sexually Transmitted Ureaplasma urealyticum Infection

Dual energy metabolism-dependent effect of Ureaplasma urealyticum infection on sperm activity.