Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation

Abstract

According to global data, there is a male reproductive potential decrease. Pathogenesis of male infertility is often associated with autoimmunity towards sperm antigens essential for fertilization. Antisperm autoantibodies (ASAs) have immobilizing and cytotoxic properties, impairing spermatogenesis, causing sperm agglutination, altering spermatozoa motility and acrosomal reaction, and thus preventing ovum fertilization. Infertility diagnosis requires a mandatory check for the ASAs. The concept of the blood–testis barrier is currently re-formulated, with an emphasis on informational paracrine and juxtacrine effects, rather than simple anatomical separation. The etiology of male infertility includes both autoimmune and non-autoimmune diseases but equally develops through autoimmune links of pathogenesis. Varicocele commonly leads to infertility due to testicular ischemic damage, venous stasis, local hyperthermia, and hypoandrogenism. However, varicocelectomy can alter the blood–testis barrier, facilitating ASAs production as well. There are contradictory data on the role of ASAs in the pathogenesis of varicocele-related infertility. Infection and inflammation both promote ASAs production due to “danger concept” mechanisms and because of antigen mimicry. Systemic pro-autoimmune influences like hyperprolactinemia, hypoandrogenism, and hypothyroidism also facilitate ASAs production. The diagnostic value of various ASAs has not yet been clearly attributed, and their cut-levels have not been determined in sera nor in ejaculate. The assessment of the autoimmunity role in the pathogenesis of male infertility is ambiguous, so the purpose of this review is to show the effects of ASAs on the pathogenesis of male infertility.

Detection of Sperm DNA Integrity and Some Immunological Aspects in Infertile Males

“…Previous data showed an effect of ASAs on actual DNA lack of the sperm cell. In the present study, the IgG and IgA antibodies were detected by the direct method according to their bounding with the sperm head and exhibited no significant difference for all samples and those of secondary type infertility (Chereshnev, et al, 2021). Nevertheless, significant correlations were noticed between the two classes of antibodies, IgG and IgA, which detected bounding to the sperm heads in subjects with primary type infertility (Ata, et al, 2021;Audu, et al, 2021).…”

“…Conflicting evidence was observed on the relationship between the presence of ASAs and sperm characteristics including concentration, motility, and morphology in the sperm (Dacheux and Dacheux, 2014). The majority of published studies found no link between the presence of ASAs and sperm concentration or motility and morphology (Chereshnev, et al, 2021). There were No.…”

“Seminal testosterone”, rising viewpoint of local spermatogenesis in nonobstructive azoospermia: One center long-term bidirectional cohort study

“…Paracrine of the testis is considered to be an important way to regulate spermatogenesis, and many cytokines, genes and proteins are involved in the paracrine pathway regulating spermatogenesis ( 26 – 29 ). In the testis, local follicle stimulating hormone, luteinizing hormone, progesterone, estradiol and progesterone are considered to be closely related to spermatogenesis ( 30 , 31 ). Comparative medicine found that the local balance between androgen and estrogen was important for spermatogenesis ( 32 ).…”

Bridging the Gap: Animal Models in Next-Generation Reproductive Technologies for Male Fertility Preservation

“…Immunological factors usually include the production of auto-anti-sperm Antibodies. Some men produce antibodies that attack their sperm, harming their fertility [1].…”