title: Functional deficit of sperm and fertility impairment in men with antisperm antibodies.
abstract: Autoimmune reactions against the sperm cells play an ambiguous role in fertility impairment. The objective of this study was to characterize functional deficit of sperm conditioned by antisperm immune response in normozoospermic men. This was a multi-centric, cross-sectional, сase-control study. The study subjects were 1060 infertile normozoospermic men and 107 fertile men. The main outcome measures were clinical examination, semen analysis including MAR test for antisperm antibodies (ASA), computer-aided sperm analysis, acrosome reaction (AR) detected with flow cytometry, DNA fragmentation measured with sperm chromatin dispersion, reactive oxygen species (ROS) assessed using the luminol-dependent chemiluminescence method. 2% of the fertile men had MAR-IgG ≥ 50%, but all subjects with MAR-IgG>12% were outliers; 16% infertile men had MAR-IgG ≥ 50% (p<0.0001). There was a direct correlation between the infertility duration and MAR-IgG (R=0.3; р<0.0001). The ASA-positive infertile men had AR disorders 2.1 times more frequently (р<0.02), predominantly inductivity disorders. We found signs of hyperactivation proportionate to the ASA level (p<0.001). DNA fragmentation was more highly expressed and was 1.6 and 1.3 times more frequent compared with the fertile and the ASA-negative patients, respectively (p<0.001 and p<0.05). We found signs of oxidative stress (OS): ROS generation by washed ASA-positive spermatozoa was 3.7 times higher than in the fertile men (p<0.00001) and depended on the ASA levels (R=0.5; p<0.0001). The ASA correlation with ROS generation in native sperm was weak (R=0.2; р<0.001). We concluded that autoimmune reactions against spermatozoa are accompanied by a fertility decrease in normozoospermia. This results from AR and capacitation disorders and DNA fragmentation. The pathogenesis of sperm abnormalities in immune infertility is associated with the OS of spermatozoa.
authors.affiliation: Department of Obstetrics, Gynecology, Perinatology and Reproduction, I.M. Sechenov First Moscow State Medical University, Oparin st. 4, 117997 Moscow, Russia; Department of Clinical Andrology, Federal State Budget Institution Peoples' Friendship University of Russia, Stavropol'skaya st. 23, 109386 Moscow, Russia. Electronic address: vbojedomov@mail.ru.
authors.forename: V A
authors.initials: VA
authors.lastname: Bozhedomov
authors.affiliation: Federal State Budget Institution "Research Center for Obstetrics, Gynecology and Perinatology" of Ministry of Healthcare of the Russian Federation, Oparin st. 4, 117997 Moscow, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Nikolaeva
authors.affiliation: Federal State Budget Institution "Research Center for Obstetrics, Gynecology and Perinatology" of Ministry of Healthcare of the Russian Federation, Oparin st. 4, 117997 Moscow, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Ushakova
authors.affiliation: Department of Clinical Andrology, Federal State Budget Institution Peoples' Friendship University of Russia, Stavropol'skaya st. 23, 109386 Moscow, Russia.
authors.forename: N A
authors.initials: NA
authors.lastname: Lipatova
authors.affiliation: Department of Clinical Andrology, Federal State Budget Institution Peoples' Friendship University of Russia, Stavropol'skaya st. 23, 109386 Moscow, Russia.
authors.forename: G E
authors.initials: GE
authors.lastname: Bozhedomova
authors.affiliation: Department of Obstetrics, Gynecology, Perinatology and Reproduction, I.M. Sechenov First Moscow State Medical University, Oparin st. 4, 117997 Moscow, Russia; Federal State Budget Institution "Research Center for Obstetrics, Gynecology and Perinatology" of Ministry of Healthcare of the Russian Federation, Oparin st. 4, 117997 Moscow, Russia.
authors.forename: G T
authors.initials: GT
authors.lastname: Sukhikh
mesh_terms: D020101:Acrosome Reaction / Q000276:immunology; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D003430:Cross-Sectional Studies; D053938:DNA Fragmentation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007248:Infertility, Male / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000276:immunology; D012189:Retrospective Studies; D013094:Spermatozoa / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D017382:Reactive Oxygen Species
keywords: Acrosome reaction; Antisperm antibodies; Normozoospermia; Reactive oxygen species; Sperm DNA fragmentation