Involvement of soluble Fas Ligand in germ cell apoptosis in testis of rats undergoing autoimmune orchitis

Dual role of immune cells in the testis

“…In rats with severe EAO, we detected increased levels of sFasL in interstitial fluid as well as an increased number of testicular CD4+ and CD8+ T cells expressing membrane-FasL (mFasL) 78 . The absence of detectable differences between cell surface and total expression of FasL by T cells supports the notion that in T cells mFasL, but not intracellular preformed FasL, could be the sole source of the soluble form released into the extracellular milieu.…”

“…We demonstrated that cytokines known to be involved in GC apoptosis such as TNF-α, IL-6 and the soluble form of FasL (sFasL) are produced in the normal rat testis 58 , 78 . We detected membrane FasL expressed by T cells but not by macrophages.…”

“…Moreover, FasL- Strep was able to induce GC apoptosis 78 . The impairment of BTB in rats undergoing autoimmune orchitis might facilitate sFasL passage into the adluminal compartment where it has the capacity to induce GC apoptosis by binding to its receptor.…”

“…In the testis, ADAM10 and 17 are expressed by pre-pubertal GCs and ADAM17 has been proposed as one of the molecules triggering GC apoptosis during the first wave of spermatogenesis 34 , 81 . T cells and also Leydig cells might be sources of sFasL present in the interstitial fluid of normal testis 78 . Intratesticular injection of FasL conjugated in its extracellular domain to Strep -Tag molecule (FasL- Strep , BioTAGnology) showed that sFasL was able to enter the STs.…”

The Immunophysiology of Male Reproduction

“…291 The pro-inflammatory cytokines, TNF and IFNγ, FAS and FASL, and NOS2 have been identified as potential causative factors in the development of orchitis, principally by stimulating antigen-presentation activity and spermatogenic cell apoptosis. 595,[890][891][892][893][894] Although IL6 production by testicular macrophages increased during experimental autoimmune orchitis in rats, 895 and was implicated in the disruption of the inter-Sertoli cell tight junctions, 896 administration of IL6 has been shown to inhibit the progression of orchitis in LPS-resistant mice. 897 The progression of orchitis may also be inhibited by IL10 and by androgens.…”