A multicenter retrospective study pointed out that the presence of live microorganisms in fresh normal semen decreases sperm motility as the amount of microorganisms increases. In patients with urethritis, prostatitis, and seminal vesiculitis, sperm motility decreases, sperm survival time is shortened, dead sperm can reach more than 50% 4 h after semen discharge, and more than 20% have coiled tail deformities. The percentage of infertility can be increased 4-fold in those with significant accessory gonadal inflammation. When the in vitro concentration of E. coli reaches 1×104/ml, it can make about 40% to 75% of sperm agglutinate at the head or tail through the two adhesion points on its surface, making the sperm vitality decrease.
Gonococcal infection and infertility
According to a group of statistics, 24 out of 1000 cases of CP patients have gonococcal infection. Gonococcal damage to the reproductive tract is more serious and has a great impact on fertility. In addition, the inflammation around the urethra caused by gonorrhea can easily form scarring to narrow the urethra and cause incomplete or retrograde ejaculation.
Chlamydia, mycoplasma infection and infertility
The effects of Mycoplasma urealyticum (UU) and Chlamydia trachomatis (CT) on semen are highly controversial. Weidner (1991) found that UU and CT did not affect the main parameters of semen analysis, and their density, viability, and morphology were not affected. However, Jiang Yunxian et al. made a study on 785 CP patients, and in the first stage 436 (76.O%) of 574 patients were positive for UU; in the second stage 96 (45.5%) of 211 patients were positive for UU and 103 (48.8)% were detected for CT, while the control group was all negative.
Another study showed that 33% were positive for Chlamydia non-bacterial prostatitis. uU causes spermatozoa to fuse with protoplasm when adsorbed on the sperm surface, allowing toxic proteins and lipid components within the uU mass to be incorporated directly into the sperm plasma membrane, thus causing sperm destruction. It can also cause severe curling of the sperm tail, which affects the normal function of sperm, and can also cause a decrease in semen volume and other malformations. UU is one of the main pathogens of non-gonococcal genitourinary tract inflammation, and in recent years, due to irregular treatment, misuse of antibiotics, mixed infections, repeated infections and chronic prolongation, mycoplasma resistance is constantly changing and drug-resistant strains are increasing, leading to increased difficulty in treating the infection.
Abnormal immune response
Abnormal humoral immunity
Patients with CP combined with infertility who promote the production of anti-sperm antibodies have significantly higher circulating and local anti-sperm antibody (AsAb) positivity rates and antibody titers than patients with general infertility. Spermatozoa are antigenic and there are a wide variety of human sperm antigens (Ag), more than 100 species have been involved, located in the plasma membrane, acrosome, nucleus, mid-segment and mitochondria of spermatozoa, which can be classified as specific and non-specific. Although the blood-testis barrier separation is important, the testicular net cannot completely protect the antigen, and the blood-epidididymal barrier separation of antigen is also incomplete. Spermatozoa can still contact with the body’s immune system through the testicular net and the blood-epidymal barrier, so the blood-testis barrier is only part of the protection mechanism, and is also protected by local immunosuppressive factors. The presence of various immunosuppressive substances in semen also plays a crucial role, such as zinc compounds, sugars, peptides, and prostaglandins, all of which have certain immunosuppressive effects.
There are many causes of elevated AsAb due to the production mechanism of anti-sperm antibodies, among which reproductive tract infections are the main cause of increased AsAb. The mechanisms of production are.
(1) Exposure of antigenic material: Infection causes incomplete closure of the prostatic tubules, reflux of prostatic fluid during ejaculation, leakage of sperm into the prostate, and removal of sialic acid covering the sperm surface by pathogenic microorganisms such as bacteria and viruses, which exposes their antigenic material and stimulates an immune response. At the same time, damage to the epithelium of the prostatic tubules during inflammation increases the permeability of immunologically active cells such as lymphocytes and macrophages in the reproductive tract, inducing the production of AsAb;
②Antigenic cross-reactivity;
③Immune regulation imbalance;
(iv) disruption of the blood-testis barrier.
Mechanisms of infertility caused by AsAb
(1) It acts directly on sperm, causing sperm agglutination, braking and decreased vitality, and semen non-liquefaction, in which cytotoxic antibodies have lethal effects on sperm. However, it only affects the function, not the number and morphology of sperm, because the antibodies secreted by the prostate gland do not come into contact with sperm until the time of ejaculation;
② Cytotoxic effect: Sperm antibodies and sperm interact with each other to activate the complement system, and with the cooperation of complement action, damage the permeability and integrity of the sperm cell membrane, causing sperm death or braking;
③Interference with sperm penetration through the cervical mucus (AsAb bound to sperm can prevent sperm from penetrating the cervical mucus and moving up;
④Interference with sperm capacitation and acrosome reaction;
⑤ Interfere with the fertilization process by preventing sperm from binding to the zona pellucida oocyte membrane;
The conditioning effect of @AsAb enhances the phagocytosis of sperm by local phagocytes in the reproductive tract;
(7) Antigen-antibody complexes are deposited in testicular tissues, affecting spermatogenic function and preventing sperm production, which is known as immune orchitis;
(viii) Interference with embryonic implantation.
Abnormal cellular immunity
The distribution of lymphocytes in the male genital tract is normal. In the male reproductive tract, T lymphocytes tend to be concentrated in the prostate, epididymis and vas deferens and are characterized by compartmentalized distribution; CD8+ subpopulations are mainly present in the lamina propria and epithelium; conversely, CD4+ subpopulations are mainly present in the mesenchymal connective tissue; the distribution of B lymphocytes is mostly confined to the prostate mesenchymal tissue, and B lymphocytes are also present in the semen. The CD8+ subpopulation is predominant in the tissue of the reproductive tract and in the seminal fluid, and the CD8+ subpopulation is predominant in areas where the blood-testis barrier is weak or absent, and where the ductal material is absorbed and the spermatozoa are stored.
CD8+ cells act as an immunosuppressive barrier to prevent an immune response to sperm autoantigens.
Abnormal cellular immunity and infertility
Prostate fluid is reduced in T cells and significantly elevated in B cells in infertile patients with prostatitis. In most infertility patients with positive serum AsAb, the lymphocyte subpopulation of the germinal tract is dominated by TH/I.(CD4+). This indicates that lymphocytes are involved in constituting the immune barrier of the male genital tract. In this case, the lymphocytes are present in an unactivated form and the immune system is in a state of “immune tolerance” due to the quantitative and distributional characteristics of the T-lymphocyte subsets in the male genital tract. When the number or function of CD8+ cells decreases and the number or activity of TH/I cells increases, the ability of self-Ts/c cells to suppress the activation of self-reactive cells decreases, and self-reactive cells become hyperfunctional and may produce AsAb.
Endocrine changes
Serum testosterone has been found to be decreased and follicular estrogen (FSH) elevated in infertile patients with prostatitis. This endocrine disorder affects male fertility and hormone levels are restored when CP is effectively treated.
Partial or complete obstruction of the vas deferens
CT can spread to other tissues and organs of the reproductive tract and produce corresponding pathological changes, such as orchitis, chronic epididymitis, epididymal fibrotic nodule formation, vasovaginitis, ejaculatory duct obstruction, etc., causing scarring adhesions, narrowing or atresia of the prostate and sperm output duct. Obstruction can occur from the varicocele to the vas deferens, resulting in obstruction of sperm output and affecting fertility.
Sexual Dysfunction
Patients with CP often experience sexual dysfunction such as impotence (ED), premature ejaculation (PH), and non-ejaculation, which affect male fertility.
1, the impact of psychological factors
Many research studies have shown that CP patients have obvious psycho-psychological burdens and changes in personality characteristics, especially in patients who have not been treated for a long time. Its main manifestations are anxiety, depression, loss of energy, fatigue, paranoia, fear of sexually transmitted diseases, insomnia and dreaminess, painful ejaculation, premature ejaculation and other symptoms¨ cited. All day long, they are worried and overwhelmed, fearing that CP will affect their sexual function and fertility. Most patients can appear sexual dysfunction such as reduced libido and affect fertility.
2, other aspects of the impact
There are many mechanisms of infertility caused by CT, but mainly the above aspects. In addition, the side effects of drugs and physical therapy used in the treatment of CP may also affect male fertility (such as anti-inflammatory drugs, hot water baths, prostate injections, vasectomies, etc.). Of course if improper treatment or over treatment is given, the effects that occur will certainly be greater as well. There is also infectious prostatitis, especially when UU, CT infection, will cause the spouse’s reproductive tract infection, if not completely treated, the couple will be long-term repeated mutual infection and make CP long lasting, making the degree of infertility further aggravated.
In summary, CP is closely related to the occurrence of male infertility, but many of its specific mechanisms are not yet well understood. With the continuous development of experimental techniques and close integration with I clinical, the mechanism of CP causing male infertility will be further elucidated.