The genitourinary microbiome, oxidative stress, DNA damage and male infertility

Ho, C., Vaughan-Constable, D. R., Ramsay, J., Jayasena, C., Tharakan, T., Yap, T., Whiteman, I., Graham, N., Minhas, S., & Homa, S. T. (2022). The relationship between genitourinary microorganisms and oxidative stress, sperm DNA fragmentation and semen parameters in infertile men. Andrologia https://doi.org/10.1111/and.14322

The inside and the outside of our bodies are teeming with microorganisms.

Somewhere around 1-3% of our body weight is made up of bacteria, fungi and other microbes, which outnumber our own cells by about 10-to-1^[1]. Everywhere we look, there are distinct populations of microbes that influence biological functions and, consequently, our health.

The seminal microbiome is “rich and diverse”^[2]. Semen, like urine^[3], is certainly not sterile.

The semen microbiomes are not profoundly different between fertile and infertile men, but when data are combined between studies, ureaplasmas are twice as likely to be found in the semen of infertile men². Several other bacterial species are associated with decreased semen quality, while Lactobacillus are associated with improved quality². Effects of the male genitourinary tract microbiome on fertility are more nuanced than simple effects on sperm count or other common semen parameters, it seems².

Oxidative stress is regarded as a fundamental pathogenic cause of male infertility. Reactive oxygen species (ROS) can impair mitochondrial and plasma membrane function, which interferes with sperm motility, capacitation and fertilisation, embryo development and, potentially, offspring health. Damage to single- and double-stranded DNA, is caused by oxidative stress, causing DNA fragmentation, which is elevated in infertile men.

A retrospective study of urine and semen samples from 770 men seeking fertility assistance in the UK, showed higher levels of ROS in semen of men with Ureaplasma spp. and Gardnerella vaginalis in their urine and Enterococcus spp. in semen^[4]. The highest ROS levels were observed in men with microorganisms detected in their urine and semen. Levels of DNA fragmentation were similarly highest in these men.

DNA fragmentation is associated with poor fertility, embryo quality and pregnancy outcomes from assisted reproduction.

The presence of some bacterial species in semen or urine may reflect dysbiosis that contributes to poor male fertility. However, colonisation by these microorganisms is likely to be otherwise unsymptomatic. Routine screening for the presence of genitourinary microorganisms that might impair fertility, such as Ureaplasma spp., Gardnerella vaginalis and Enterococcus spp., may be a future component of routine care for couples seeking fertility assistance. This may allow targeted antibiotic treatment to improve reproductive outcomes⁴.