Impaired Spermatogenesis in Infertile Patients with Orchitis and Experimental Autoimmune Orchitis in Rats

AMARILLA, MARÍA SOFÍA; GLIENKE, LEILANE; MUNDURUCA PIRES, THAISY; SOBARZO, CRISTIAN MARCELO; OXILIA, HERNÁN GUSTAVO; FULCO, MARÍA FLORENCIA; RODRÍGUEZ PEÑA, MARCELO; MAIO, MARÍA BELÉN; FERRER VIÑALS, DENISSE; LUSTIG, LIVIA; JACOBO, PATRICIA VERÓNICA; THEAS, MARÍA SUSANA

Biology

MDPI

Lugar: Basel; Año: 2024 vol. 13

Experimental autoimmune orchitis (EAO) is a well-established rodent model of organspecific autoimmunity associated with infertility in which the testis immunohistopathology has beenextensively studied. In contrast, analysis of testis biopsies from infertile patients associated withinflammation has been more limited. In this work, testicular biopsies from patients with idiopathicnon-obstructive azoospermia diagnosed with hypospermatogenesis (HypoSp) [mild: n = 9, andsevere: n = 11], with obstructive azoospermia and complete Sp (spermatogenesis) (control group,C, n = 9), and from Sertoli cell-only syndrome (SCOS, n = 9) were analyzed for the presence ofimmune cells, spermatogonia and Sertoli cell (SCs) alterations, and reproductive hormones levels.These parameters were compared with those obtained in rats with EAO. The presence of increasedCD45+ cells in the seminiferous tubules (STs) wall and lumen in severe HypoSp is associated withincreased numbers of apoptotic meiotic germ cells and decreased populations of undifferentiatedand differentiated spermatogonia. The SCs showed an immature profile with the highest expressionof AMH in patients with SCOS and severe HypoSp. In SCOS patients, the amount of SCs/ST andKi67+ SCs/ST increased and correlated with high serum FSH levels and CD45+ cells. In the severephase of EAO, immune cell infiltration and apoptosis of meiotic germ cells increased and the number of undifferentiated and differentiated spermatogonia was lowest, as previously reported. Here, we found that orchitis leads to reduced sperm number, viability, and motility. SCs were mature (AMH-) but increased in number, with Ki67+ observed in severely damaged STs and associated with thehighest levels of FSH and inflammatory cells. Our findings demonstrate that in a scenario wherea chronic inflammatory process is underway, FSH levels, immune cell infiltration, and immaturephenotypes of SCs are associated with severe changes in spermatogenesis, leading to azoospermia. Furthermore, AMH and Ki67 expression in SCs is a distinctive marker of severe alterations of STs in human orchitis.