Endogenous Galectin-1 controls testicular pathology through modulation of germ cells apoptosis

PEREZ, C.V.; GOMEZ L.; GUALDONI G.; RABINOVICH G.; LUSTIG L.; GUAZZONE V.A.

Boston

Congreso; 14th International Symposium for Immunology Reproduction (ISIR); 2013

International Society for Immunology of Reproduction

Galectins, a family of evolutionarily conserved glycan-binding proteins, play critical roles in multiple biological processes including host?pathogen interactions, immune cell signaling and activation, T cell homeostasis, preservation of fetomaternal tolerance and regulation of autoimmune pathology. Galectin-1 (Gal-1), a member of this protein family, is highly expressed in immune privileged sites, including the testis, where it is distributed in Sertoli, peritubular, and Leydig cells. However, the in vivo role of endogenous Gal-1 in this organ has not yet been explored. Experimental autoimmune orchitis (EAO) is an experimental model useful to study the autoimmune basis of testicular inflammation associated with subfertility and infertility. EAO was induced in wild type (wt) mice and in mice genetically deficient in Gal-1 (Lgals1−/−) by immunization with testicular antigens in complete Freundʹs adyuvant and Bordetella pertussis. A significant decrease in EAO incidence and a reduced severity of the disease was observed in Lgals1−/− mice versus the wt group (mean EAO score: Lgals1−/−, 7.07±0.70; wt, 14.74±2.19). Testicular histopathology showed that wt group presented multifocal testicular damage characterized by an interstitial lymphomononuclear cell infiltrate and different degrees of germ cell sloughing of the seminiferous tubules. Analysis of apoptosis of paraffin embedded testis sections by using a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay and evaluating the expression of the active form of caspase 3 protein revealed that the predominant cell types positive for TUNEL and immunoreactive for caspase 3 in mice with EAO were spermatids and spermatocytes, mainly localized in the adluminal compartment of seminiferous. A significant increased number of TUNEL-positive germ cells was detectable in testis from wt mice compared with Lgals1−/− mice or with normal (N) untreated group (number of positive germ cells/100 tubules: wt, 81,17±25,97; Lgals1−/−,, 3,80±1,72; N, 6,00±3,26). These results unveil a novel role for galectin-1 as a promoter of inflammatory testicular pathology and suggest that, in particular in the testis, the pro-apoptotic function of Gal-1 on germ cells prevails over its known immunosuppressive activity.