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

Area of Science:

• Reproductive Immunology
• Andrology
• Pathology

Background:

• Experimental autoimmune orchitis (EAO) is a rodent model for studying testicular autoimmunity and infertility.
• Analysis of human testicular biopsies in infertile patients with inflammation is limited.
• Understanding immune cell roles in testicular dysfunction is crucial for infertility research.

Purpose of the Study:

• To compare immune cell presence, Sertoli cell (SC) alterations, and hormone levels in human testicular biopsies with EAO.
• To investigate the relationship between inflammation, SC phenotype, and spermatogenesis in hypospermatogenesis (HypoSp) and Sertoli cell-only syndrome (SCOS).
• To identify markers of severe testicular damage in human orchitis.

Main Methods:

• Analyzed testicular biopsies from patients with mild/severe HypoSp, obstructive azoospermia (control), and SCOS.
• Assessed immune cells (CD45+), apoptotic germ cells, spermatogonia, Sertoli cells (SCs), and hormone levels (FSH).
• Compared human data with findings from rats with EAO.

Main Results:

• Severe HypoSp showed increased CD45+ cells, germ cell apoptosis, and decreased spermatogonia.
• SCOS and severe HypoSp exhibited immature SCs (high AMH), correlating with high FSH and CD45+ cells.
• EAO model showed increased immune cells, germ cell apoptosis, and reduced spermatogonia, with mature SCs (low AMH) but increased numbers in damaged tubules.

Conclusions:

• Chronic inflammation, elevated FSH, immune cell infiltration, and immature SC phenotypes are linked to severe spermatogenesis impairment and azoospermia in humans.
• AMH and Ki67 expression in SCs serve as distinctive markers for severe testicular alterations in human orchitis.
• Orchitis significantly reduces sperm count, viability, and motility.