Dor several years, the observations on the evolution of the quality of the sperm worry as much as it seems to go hand in hand with a fertility rate in fall. A decline that has become a global concern…
One of the most crucial questions is whether this decline is explained solely by economic and behavioral factors, or whether biological factors may also be involved.
The causes are complex.
Declining sperm quality is part of a larger trend of deteriorating male reproductive health, which is beginning to escalate into a general fertility crisis. If it is already established that environmental factors negatively influence the quality of sperm, to fully understand the situation, understanding the biology of spermatozoa remains a crucial issue: with the impact of the cellular environment, they still reserve unknowns. .
Initially considered as parasites contained in the semen, half worms half eels, spermatozoa were isolated and then recognized as cellular players in male reproduction in the 17th century. But they are not the only ones… For several years, scientific circles have noticed that other cells, non-human this time, would play a role alongside them in human fertility.
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The microbiota in us
Countless microorganisms (bacteria, yeasts, fungi and viruses) live in all multicellular organisms. They constitute real ecosystems called a microbiota, and whose physiological functions have been a subject of study for twenty years.
These micro-organisms live in colonies within many tissues: digestive and respiratory systems (which are particularly studied and well known to the general public), but also nose, skin, etc. Weighing 2 to 3 kg in an adult, these microbial communities are intriguing. And they are all the more interesting because they give everyone unique characteristics and are likely to vary during an individual’s life. They would therefore be associated, for some, with good health and increased longevity.
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Launched in 2008, the Human Microbiome Project aims to characterize the diversity of these sets of microorganisms and to explore the link between the presence or variation of these communities and the development of diseases. Nearly 40,000 articles have been written between 2009 and 2021 on the intestinal microbiota, which constitutes the largest mass of the microbiota of an adult individual.The discovery of the physiological importance of these microbiota has changed our relationship to health and opened up new therapeutic perspectives. The scientific community has therefore begun to explore the microbiota of other tissues, less studied in first intention.
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The sperm microbiota, this unknown
Sperm and the testicular environment are not sterile, in both senses of the word: they naturally contain many microorganisms. Less rich but more diversified than the vaginal microbiota, it is enriched or altered during an individual’s life. These two microbiota are of particular interest in human fertility studies.
The comparative analysis of more than fifty studies has in fact highlighted the complexity and modifications of the sperm microbiota.
Initially estimated by culture techniques, microbiota are now analyzed using molecular biology techniques to access bacterial genomes. High-throughput genome sequencing techniques as well as advances in bioinformatics contribute to the characterization and analysis of these ecosystems of microorganisms and their relationships with the state of health of their respective hosts.
These two methods of analysis were able to highlight the existence of different types of bacteria in the semen of fertile and non-fertile subjects.
Culture methods frequently observe the presence of Staphylococci, Enterococci,Escherichia and D’Ureaplasma. Sequencing methods report an abundance of Lactobacilli, Prevotella, Pseudomonas as well as other opportunistic anaerobic pathogens (micro-organisms living in an environment without oxygen).
These results undoubtedly illustrate the limits of these detection methods, but leave no doubt about the fact that spermatozoa are not alone in ejaculates…
What origin and what impact for the sperm microbiota?
Two origins are allowed. One involves the upper genital tract (including the prostate), the other tissues foreign to the urogenital system (the digestive tract, the oral cavity, the blood or the vagina), the sharing of microbiota between the two can occur through sexual relations.
Several studies report a correlation between the presence of particular microbes and the quality of sperm. For example, they would be capable of adhering to spermatozoa and, therefore, of modifying their functions – such as mobility, until they are immobilized.
The reported effects are very variable… The presence of lactobacilli would thus be favorable to the functions of spermatozoa, while the presence of proteobacteria,Anaerococcus and of Bacteroides ureolyticus would be more associated with lower quality sperm. How can these different impacts on sperm functions be explained?
First possibility, micro-organisms could have a positive effect on the functions of the testicle itself… But, second hypothesis, they could act as antioxidants: they would reduce the concentration of reactive oxygen species (or reactive oxygen species , the excess of which can damage cellular structures) and would therefore reduce the fragmentation and alteration of DNA.
The supply of live micro-organisms, in the form of probiotics, shows beneficial effects on sperm motility in rabbits. In humans, supplementation of the diet Lactobacillus and Bifidobacterium increases motility and decreases DNA fragmentation in individuals with asthenozoospermia (decrease or absence of sperm motility, for more than 50% of them one hour after ejaculation).
More recent studies of probiotic administration have also shown improvements in sperm concentration and motility as well as decreases in cell death or inflammation markers. However, these observations were not made on populations large enough for clear conclusions to be drawn…
Sperm and the vaginal microbiota
Once they have entered the female genital tract, the spermatozoa must also confront the existence of the local microbiota…
Few studies have been carried out on the effects of this other microbiota on sperm, but several results nevertheless indicate that vaginal bacteria can have deleterious effects on the survival of spermatozoa. Thus, if the lactobacilli would rather have a protective effect in the male genital tract, their massive presence in the vagina alters the quality of the sperm and phenomena of adhesion and agglutination of the spermatozoa are observed.
Other cellular mechanisms can be triggered such as the reduction in cell motility or the destruction of spermatozoa by apoptosis. This programmed cell death could be caused either by interaction between bacterial molecules and the surface of the acrosome of the spermatozoon (at the level of its head), or by the alteration of its membrane.
It has been suggested that the vaginal microbiota may act by discriminating against sperm of lower quality, since the latter would be more sensitive to bacteria hosted by the female genital tract.
Ways forward
Knowing the seminal microbiota and its modifications would make it possible to better understand the impact of this environment on the quality of spermatozoa: can these bacteria have a real beneficial effect on sperm quality? Depending on their nature, can these microbiota promote or harm male fertility?
The sperm microbiota tends to be increasingly recognized as a potential cause of infertility, but too few studies have focused on these aspects – which therefore remain controversial.
It is therefore necessary to remain cautious and to resolve the hypothesis offered by these studies: if the presence of microbiota is sometimes correlated with pathological states, the cause and effect relationship has not been clearly established. Exploration of the biological mechanisms of this spermatozoid-microbe companionship is therefore only beginning… It already offers, despite everything, new diagnostic or therapeutic avenues for non-fertile couples.
* Jean-François Bodart, University Professor, Cell Biology and Developmental Biology, University of Lille