Expression of Interferons-  and -  in Testicular Interstitial Tissue and Spermatogonia of the Rat

Abstract

The testis is divided into two compartments: the seminiferous tubules and the interstitial tissue. The latter essentially consists of the blood and lymphatic vessels, testosterone-producing Leydig cells, and testicular macrophages. In the exploration of the testicular antiviral defense system, we initially searched for interferon (IFN) production by the seminiferous tubule cells. The site of virus entry into the testis is probably the interstitial compartment; thus, it is important to know whether and how the cells in this compartment are protected against viral infection. In addition, as germ cell precursors (spermatogonia) are only partially protected by the blood-testis barrier, it was important to explore the antiviral capability of these cells. In this study we searched for IFN production by Leydig cells, testicular macrophages, and spermatogonia after exposure to Sendai virus. We also investigated the effect of viral exposure on testosterone production by Leydig cells. Our results show that spermatogonia do not constitutively express IFNs and give a very poor response to the virus. In contrast, testicular macrophages constitutively produced type I IFNs, and this production was markedly stimulated by Sendai virus. Leydig cells produced twice as much type I IFNs as testicular macrophages after viral exposure, and they were the only cells producing both IFNalpha and -gamma, with these IFNs being dramatically induced/ increased in response to exposure to the virus. Furthermore, incubation of Leydig cells with the Sendai virus stimulated testosterone production. In conclusion, this study further establishes the topography of IFN expression within the testis. This allows us to hypothesize that the potential antiviral system represented by Leydig cells and, to a lesser extent, by macrophages plays a key role in protecting both androgen production and spermatogenesis.

Testicular defense systems: immune privilege and innate immunity

“…The testicular innate antiviral responses have been previously demonstrated based on a series of pioneering studies on the expression and regulation of both interferons (IFNs) and antiviral proteins in the testis by Professor Jégou's group. [60][61][62]95,96 These investigators also showed that several defensins are expressed in murine and human testes, and may contribute to the innate antimicrobial defense. 97 Recent studies have revealed that various PRRs are abundantly expressed in testicular cells and initiate testicular innate immune responses.…”

“…59 Previous studies demonstrated that rat Leydig cells exhibit innate antiviral ability in response to viral infection. 60,61 Human Leydig cells show relatively weak antiviral activity compared with rat cells. 62 These observations raise an interesting question whether the human testis has a weaker innate defense system against viral infection compared with the murine testis.…”

Viruses in the Mammalian Male Genital Tract and Their Effects on the Reproductive System

“…The basal tubular position of these germ line precursors, a priori, exposes them to the risk of contamination in cases of viral infection. Despite the high potential risk of infection of spermatogonia, these cells do not constitutively express biologically active IFNs, and they respond only weakly to stimulation by Sendai virus in vitro (89). Similarly, early spermatids and pachytene spermatocytes, although expressing low levels of IFNs under basal conditions, respond very weakly if at all to exposure to Sendai virus (88).…”

Expression of alpha and gamma interferon receptors in the sperm cell

“…IFN-␣ and IFN-␥ are expressed in the testes (Dejucq et al, 1995(Dejucq et al, , 1998 and the hyperexpression of IFN-␣ and IFN-␤ in transgenic murine testes leads to infertility (Hekman et al, 1988;Iwakura et al, 1988). In contrast, administration of IFN-␣ enhances spermatogenesis in some infertile men increasing sperm number in the semen (Yamamoto and Miyake, 1994).…”