Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 6 October 2021 / Approved: 7 October 2021 / Online: 7 October 2021 (11:40:21 CEST)

A peer-reviewed article of this Preprint also exists.

Chereshnev, V.A.; Pichugova, S.V.; Beikin, Y.B.; Chereshneva, M.V.; Iukhta, A.I.; Stroev, Y.I.; Churilov, L.P. Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation. Pathophysiology 2021, 28, 471-489. Chereshnev, V.A.; Pichugova, S.V.; Beikin, Y.B.; Chereshneva, M.V.; Iukhta, A.I.; Stroev, Y.I.; Churilov, L.P. Pathogenesis of Autoimmune Male Infertility: Juxtacrine, Paracrine, and Endocrine Dysregulation. Pathophysiology 2021, 28, 471-489.

Abstract

According to global data, there is a male reproductive potential decrease. Pathogenesis of male infertility often is 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, thus preventing ovum fertilization. Infertility diagnosis requires mandatory check for the ASAs. The concept of blood-testis barrier currently is re-formulated with emphasis of informational paracrine and juxtacrine effects, rather than simple anatomical separation. Aetiology 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 blood-testis barrier facilitating ASAs production as well. There are contradictory data on the role of ASAs in 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. Diagnostic value of various ASAs was not yet clearly attributed, and their cut-levels not agreed neither in sera nor in ejaculate. The assessment of the autoimmunity role in pathogenesis of male infertility is ambiguous.

Keywords

male infertility; varicocele; varicocelectomy; spermatozoa; sperm antigens; antisperm autoantibodies; ejaculate; orchitis; autoimmune thyroiditis

Subject

Medicine and Pharmacology, Pathology and Pathobiology

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