Study of chronic prostatitis affecting male fertility
Chronic prostatitis (CP) is a common disease of the male genitourinary system, often combined with infections of the seminal vesicles, epididymis and other genital tracts, and is a common infectious disease of the accessory gland in young adults.
Collins (USA) and Nicke (Canada) reported a prevalence of 16% and 9.7% in the male population, respectively; Kunishima (Japan) and Cheah (Malaysia) reported a prevalence of 5% and 8.7%, respectively.
According to the National Institutes of Health (NIH), the disease has a histological detection rate of 44% to 100% in the prostate and a clinical prevalence of 5% to 50%. Some data indicate that the incidence of CP is 35% in men aged 20 to 45 years, when men are at their peak fertility, and thus, the potential threat to male fertility is very clear.
Male reproductive activity is a complex physiological process with many components that are regulated neurologically and endocrinologically, and disruption of any one of these components may have an impact on fertility.
The majority of scholars now believe that there is a close relationship between CP and male infertility. CP can change the composition of the prostatic fluid, whether bacterial or non-bacterial prostatitis, and its bacteria or inflammatory cells can be mixed in the semen with the secretion of the prostatic fluid, affecting the activity of sperm and its function through direct and indirect effects.
I. The impact of pathogenic microorganisms on infertility
1, anaerobic bacteria. The current study tends to consider anaerobic bacteria as one of the causes of male infertility. By culturing bacteria in the prostate massage fluid (EPS) of patients with chronic bacterial prostatitis (CBP) and counting their colony-forming units, the detection rate of anaerobic bacteria was found to be 3.9 times higher than that of aerobic bacteria; polymerase chain reaction (PCR) and DNA sequence analysis techniques were used to improve the detection rate of bacteria in semen, and it was found that 90% of the samples were anaerobic bacteria are the main pathogenic bacteria of CBP.
The study confirmed that anaerobic bacteria can reduce the penetration of sperm to the eggs of voles, and concluded that anaerobic bacteria are not only the causative agent of CBP, and are related to infertility caused by CBP; anaerobic CBP can cause semen liquefaction disorder and increase the number of heterogeneous sperm, which eventually lead to infertility.
2, aerobic bacteria. Bacteria can be mixed into semen with the secretion of CBP glandular fluid, leading to changes in sperm activity parameters through intercellular interactions and adhesion phenomena, and interfering with the molecular structure and cellular integrity of sperm. Inflammation can induce dysfunction of prostate secretion, leading to poor semen liquefaction, which may be related to a decrease in prostate secretion of enzymes related to semen liquefaction during CBP.
The literature reports that the most common aerobic bacteria in EPS of CBP patients are Gram-negative rods, such as Escherichia coli and Proteus mirabilis, with E. coli accounting for about 80% . E. coli infections account for approximately 5% to 10% of CBP patients. Analysis by CASA technique revealed that E. coli infection caused a significant decrease in sperm linear motion, linear motion rate and average motion rate, and very few sperm moved forward, accounting for only 1.8%.
E. coli can also cause ultrastructural changes in the plasma membrane and other surface structures of human sperm, the head including the acrosome, resulting in defects in the head, body and tail of sperm, reducing motility and fertility.
Specific infections of CP can include Trichomonas, fungi, viruses, chlamydia, mycoplasma, etc. It is controversial that the pathogens of chronic non-bacterial prostatitis can cause male infertility, but more recent reports in the literature tend to support this view, especially with regard to Ureaplasma urealyticum (UU) infection.
Since 1974, when Gnarpe isolated UU from semen specimens of a group of patients with unexplained infertility and suggested that its infection was associated with male infertility, it has attracted the attention of scholars worldwide. Studies have shown that the detection rate of UU in the semen of male infertility patients is 40% to 58%, which is significantly higher than that of 10% to 31% in normal fertility.
UU can invade the mucosal epithelium of the reproductive tract and gonadal epithelium, affecting epithelial cell metabolism and nucleic acid synthesis, thus causing acute, chronic and subclinical infections of the reproductive organs, resulting in a decrease in semen quality and sperm function. The spermatozoa are also subject to increased sperm destruction, decreased viability and increased malformation rate.
It was observed by scanning electron microscopy and immunoenzymatic staining that UU can adsorb to the head and tail of sperm, causing sperm bloat and increased resistance, producing antisperm antibodies, agglutination, and decreased viability. By applying CASA and other techniques, the results showed that the positive rate of UU culture gradually increased with the weakening of sperm viability, the decrease of number, the increase of mortality and the increase of semen viscosity, and it is believed that UU affects the quality of semen.
Second, the effect of oxygen free radicals on infertility
The semen of CP patients contains a large number of leukocytes, and studies have shown that it can damage the function of sperm through the activity of antioxidants, and leukocytes make the penetration of sperm decrease. The seminal plasma of normal men contains low levels of free oxygen radicals (ROS), whereas in 40% to 80% of infertile patients, the level of ROS in seminal plasma is significantly higher. In bacteriospermia, activated granulocytes release large amounts of ROS, which affect fertility through the following mechanisms
1. ROS inhibit ATP production and sperm motility. The content of ATP in sperm parallels the forward motion of sperm. ROS were found to significantly inhibit sperm ATP production and reduce sperm motility by chemical fluorescence and electron magnetic resonance. The major role of ROS is played by H2O2, which can inhibit oxidative phosphorylation of sperm mitochondria at low concentrations and interfere with sperm energy metabolism, leading to the cessation of sperm motility. In addition, superoxide dismutase can also affect the metabolism of spermatozoa.
2, ROS produces lipid peroxides that damage the sperm plasma membrane. Human sperm plasma membranes contain large amounts of unsaturated fatty acids, while the cytoplasm contains only low concentrations of antioxidant enzymes and is therefore vulnerable to damage by lipid peroxidation. Excessive levels of ROS can damage unsaturated fatty acids in the sperm plasma membrane by inducing the production of lipid peroxides, causing the sperm membrane to lose fluidity and sperm motility to decrease, resulting in the failure of sperm-egg fusion.
3. ROS damages sperm DNA. modern studies have shown that ROS can cause cross-linking of sperm chromosomes, oxidation of DNA bases and DNA strand breakage. The ROS in the EPS of CP patients is higher than normal, and the ROS of EPS leukocyte-positive patients is higher than that of leukocyte-negative patients, indicating that the semen of CP patients is strongly oxidizing, and the abnormal oxidizing ability of semen is related to male infertility regardless of the presence or absence of leukocytes in semen.
Third, the effect of immune mechanism on infertility
1. Humoral immunity. Since the discovery of the presence of IgG and IgA in the normal prostate fluid, the immune response caused by prostatitis that leads to infertility has attracted a lot of attention. Immune activation leads to an abnormal increase in anti-sperm antibodies (AsAb) in patients with infertility.
Studies have demonstrated that AsAb can cause infertility in several ways.
(1) Affecting sperm motility.
(2) Blocking sperm capacitation.
(3) Blocking sperm migration to the cervical canal.
(4) Blocking the acrosome reaction.
(5) preventing sperm from penetrating and lysing the egg zona pellucida.
(6) Blocking sperm-egg union.
Modern research has found that the production of anti-sperm antibodies is related to chronic prostatitis, and that the level of AsAb in seminal plasma is higher than that in plasma in CP infertility patients, suggesting that AsAb is more easily produced locally in the reproductive tract, and it is believed that the detection of AsAb in plasma is more clinically meaningful. asAb attaches to the surface of sperm, mainly concentrating on the head and tail of sperm, causing serious effects on sperm motility. It has a serious impact on sperm motility and eventually leads to infertility.
2. Cellular immunity. Except for non-inflammatory pelvic pain syndrome (type IIIB prostatitis), both bacterial and non-bacterial prostatitis have inflammatory cells in their prostate fluid, mainly polymorphic leukocytes, lymphocytes, macrophages, etc. Inflammatory cells are capable of producing a variety of cytokines, such as T lymphocytes that produce interleukin-2 (IL-2) and interleukin-6 (IL-6), and macrophages that produce cyto-necrosis factor (TNF-α), interleukin IL-1β and IL-8.
TNF-α and IL-1β are markers of inflammatory infection in chronic prostatitis. It has been shown that TNF-α is an important cytokine that initiates apoptosis and impairs the binding of sperm to egg zona pellucida, thus affecting sperm-egg binding. Cytokines can directly or indirectly affect the function of sperm and induce an increase in apoptosis of spermatogenic cells, affecting fertility.
Fourth, the effect of zinc secreted by the prostate on infertility
There are many studies that have found a close relationship between trace elements and human reproductive function.
Zinc has an important role in the prostate gland, (1) maintaining the prostate’s ability to resist infection. The literature reports that normal prostate fluid contains a powerful antibacterial active protein, a zinc-containing compound, and that its level decreases in prostatitis. (2) regulates the activity of 5α-reductase present in the mitochondria and nucleus of prostate cells to regulate intracellular dihydrotestosterone levels; (3) maintains the structural integrity of macromolecules and regulates protein and nucleic acid metabolism as well as ATP production and mitochondrial function.
Zinc deficiency in the prostate can inhibit the conversion of testosterone to dihydrotestosterone, leading to gonadal dysfunction. Androgens play a major role in regulating the zinc-secreting function of the prostate to ensure that semen contains adequate zinc concentrations.
Zinc has important roles in sperm.
(1) Zinc in seminal plasma is involved in the composition of many enzymes in the reproductive system, delays lipid oxidation in sperm cell membranes, maintains the stability and permeability of the cell membrane structure, and enables sperm to have good motility.
(2) Spermatozoa absorb zinc within seminal plasma during ejaculation and bind to the sulfhydryl group of chromatin in the cell nucleus, saving chromatin from overgrowth depolymerization and facilitating fertilization.
(3) Zinc is closely related to the motility of spermatozoa. Studies have shown that this change in sperm from immobility to motility during ejaculation may be induced by zinc.
The study found that the zinc content of prostatic fluid in patients with prostatitis decreased significantly, while their plasma zinc levels were normal. It is believed that the decrease in zinc content of prostatic fluid is due to the impaired uptake and secretion of zinc by prostate tissue cells.
The significant decrease in zinc content in semen of patients with chronic prostatitis may also be due to the inflammation that affects the secretory function of the prostate tissue, and it is possible that the zinc content of semen may return to normal levels in such patients as long as the inflammation of the prostate is thoroughly treated.
Chronic prostatitis can lead to sexual dysfunction, manifested as erectile dysfunction (ED), premature ejaculation (PE), non-ejaculation, and loss of libido.
Studies have shown that 47.5% of CP patients have varying degrees of PE, while prostate disease and ED are even more closely related, with a study in Finland reporting a 43% incidence of ED and 24% of hypoactive sexual desire in patients with symptomatic prostatitis and a 17% fear of prostate cancer.
Chronic prostatitis causes sexual dysfunction for the following reasons.
(1) Patients with chronic prostatitis are overly concerned about their condition or have varying degrees of anxiety, depression and fear due to perineal discomfort and prolonged treatment, causing psychological erectile dysfunction.
(2) Infiltration of inflammatory cells causes inflammation and edema in the posterior urethra, seminal vesicles, and even the vas deferens and epididymis, causing changes in the sensitivity of locally distributed sympathetic and parasympathetic nerve endings and changes in excitation thresholds, resulting in painful, delayed, or non-ejaculation of ejaculation.
(3) Inflammatory lesions of prostatitis can cause increased tone of adrenergic nerves on the prostate envelope, which radiologically causes excitation of the ejaculatory center, leading to premature ejaculation.
(4) The prostate can regulate the secretion of a variety of hormones, such as thyrotropin-releasing hormone, adrenocorticotropic hormone, relaxin, endorphins, prolactin (PRL) and inhibin, which can have an effect on sexual function. Sexual dysfunction may also lead to a decrease in male fertility.
In summary, there is ample evidence that chronic prostatitis is closely related to the development of male infertility, and therefore, high priority should be given to the treatment of infectious factors while treating patients with male infertility.
At present, the exact mechanism by which chronic prostatitis causes infertility is not fully understood. With the continuous improvement and development of clinical and experimental techniques, further elucidation of the relationship between chronic prostatitis and male infertility is of great significance for the treatment of chronic prostatitis and the improvement of male reproductive health.