title: Vacuolar-ATPase isoform a2 regulates macrophages and cytokine profile necessary for normal spermatogenesis in testis.
abstract: a2V is required for maturation of sperm. The decreased expression of a2V at the feto-maternal interphase causes poor pregnancy outcome. The present study examined the role of a2V in spermatogenesis and inflammatory network in the testis. A single dose of anti-a2V mouse IgG or mouse IgG isotype (3 μg/animal) was injected i.p. into male mice on alternate days for 10 days. Anti-a2V-treated males exhibit severe deficiencies of spermatogenesis, which is indicated by the presence of less numbers of postmeiotic cells. Sperm counts and sperm motility were reduced significantly in anti-a2V-treated males. The release of the cleaved a2NTD was significantly lower in anti-a2V-treated testes. The TMs were identified as M2-like macrophages, and this population and the expression of various cytokines/chemokines (Tgf-β, Il-6, Nos2, Tnf, Lif, Mcp1, Ccl5) were decreased significantly in anti-a2V-treated testis compared with control testis. Moreover, the cleaved a2NTD acts as a key mediator of TMs and significantly up-regulates the secretion of testicular cytokines/chemokines, which are associated with normal spermatogenesis. When these anti-a2V-treated males were used for mating with normal females, the number of implantation sites was decreased significantly in the females mated with anti-a2V-treated males than the females mated with control males. These observations suggest that a2V plays a crucial role in spermatogenesis by regulating testicular immune responses, and its inhibition in males leads to poor pregnancy outcome in females.
authors.affiliation: Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; and.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jaiswal
authors.affiliation: Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; and.
authors.forename: Gajendra K
authors.initials: GK
authors.lastname: Katara
authors.affiliation: Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; and.
authors.forename: Timothy
authors.initials: T
authors.lastname: Mallers
authors.affiliation: U976 Institut National de la Santé et de la Recherche Médicale/Centre National de la Recherche Scientifique, St. Louis Hospital, Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Chaouat
authors.affiliation: Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; and.
authors.forename: Alice
authors.initials: A
authors.lastname: Gilman-Sachs
authors.affiliation: Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA; and kenneth.beaman@rosalindfranklin.edu.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Beaman
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D005260:Female; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D013081:Sperm Motility / Q000276:immunology*; D013091:Spermatogenesis / Q000276:immunology*; D013737:Testis / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D025262:Vacuolar Proton-Translocating ATPases
keywords: Nos2; Tgf-β; a2NTD; pregnancy loss