Semen culture and microbiological examination: The role of pathogens in male fertility and male reproductive health

Ioannis Chrysanthopoulos, B.Sc, M.Sc, Reproductive Biologist - Molecular Biologist

A justified 15% of male infertility cases are attributed to a male genital tract infections (MGTI), which is the third most common cause of male infertility after idiopathic infertility and varicocele. Pathogenic microorganisms are responsible for the most common disorders of the genitourinary system, such as prostatitis, epididymitis, orchitis and urethritis. Prostatitis and epididymitis can cause obstruction of the ejaculatory ducts, leading to oligozoospermia or azoospermia. The infection may also spread to the testis, causing testicular inflammation associated with high infertility rates and even testicular atrophy and cessation of spermatogenesis. It has been established through scientific studies that all -common and not- pathogens can cause damage to both the testicles and the epididymis, affecting both sperm quality and spermatogenesis.

However, the presence of microorganisms in the male reproductive system may remain asymptomatic for long periods of time, affecting the overall reproductive potential of the man and without other visible signs during the examination of the semen / semen analysis (increased concentration of white blood cells, increased pH, increased viscosity, presence of mucus). In particular, it has been shown that in about 50% of men the presence of microorganisms causes inflammation that remains asymptomatic, and this percentage seems to be even higher in young and sexually active men. Without proper testing, these asymptomatic inflammations can remain undetected and untreated, potentially leading to serious complications and/or infertility, and pathogens can also be transmitted to the sexual partner(s) through sexual intercourse.

The most common pathogens in the male genital tract are ureaplasma (Ureaplasma urealyticum), mycoplasma (Mycoplasma hominis/genitalium), enterobacteriaceae (Enterococcus), E. coli (Escherichia coli), staphylococcus aureus, gonorrhea (Neisseria gonorrhoeae) and chlamydia trachomatis (Chlamydia trachomatis). Ureaplasma, mycoplasma, enterococcus and E. coli are the main sources of inflammation and often adversely affect the environment of spermatogenesis through an increase in white blood cells in the genital tract. E. coli in particular, has been shown to be associated with both the development of epididymo-orchitis and prostatitis in 65%-80% of cases.

Enterococcus, E. coli, S. aureus, ureaplasma and mycoplasma have been found to negatively affect many sperm parameters, such as sperm concentration and motility, as well as their mitochondrial membranes. This observation has been highlighted by multiple studies comparing the reproductive potential of men who were positive for microorganisms compared to the parameters of men who were pathogen-free during semen culture. At the same time, different pathogens may be implicated in different negative aspects of fertility, for example, while the presence of ureaplasma may affect the concentration, motility and vitality of spermatozoa, mycoplasma seems to affect only the vitality markers, causing low sperm functionality.

The presence of pathogens in the male reproductive tract in many cases also activates the normal immune response by producing high concentrations of white blood cells that are detected in the semen. According to the World Health Organization manual (WHO, 2021), leukocytospermia is defined as the presence of white blood cells in the ejaculate at a concentration of more than 1,000,000 cells/ml and is estimated to be found in 10%-20% of infertile men, negatively affecting fertility. In the semen, white blood cells are involved in the induction of an inflammatory response to eliminate pathogens and apoptosis of immature or abnormal spermatozoa through phagocytosis and production of oxygen free radicals (ROS). In cases of leukocytospermia, the concentration of ROS can be as much as 1000 times higher than the concentration normally released by spermatozoa, which leads to increased rates of fragmentation of the genetic material (DNA) of spermatozoa.

In conclusion, the presence of pathogens in the reproductive system may be accompanied by symptoms and signs during semen examination, but may also exist without any accompanying signs. Whether at the level of genital tract infection or at the level of “silent inflammation”, and depending always on the identification of the pathogen, the implications are potentially significant and concern the whole axis of fertility and the general health of the reproductive system. In this context, conventional semen culture, as well as specialized microbiological testing and molecular testing (PCR), can offer a clear diagnosis and can directly help in the management and treatment of any type of inflammation caused by pathogens, but also more broadly enhance the preservation of fertility dynamics and reproductive health in men.


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