Neonatal testicular cell transplantation restores murine spermatogenesis damaged in the course of herpes simplex virus-induced orchitis

Abstract

Genital tract infection and inflammation may affect male fertility, causing germ and Sertoli cell loss. We determined if testicular cell transplantation is effective at repairing testicular injury induced by herpes simplex virus (HSV) orchitis. ROSA26 mice were used as donors and the recipients were C57BL/6 mice after HSV testicular inoculation; some of the recipients were treated with the antiviral drug acyclovir (ACV). ACV reduced the amount of HSV antigen in testes on Day 3 after transplantation and enhanced the efficacy of transplantation at Day 30. In recipient testes, donor Sertoli cells formed new seminiferous tubules; significantly more new tubules were observed in the testes of ACV-treated mice compared with mice not treated with ACV (17.8% vs 3.6%). Over half (50.4%) of new tubules in ACV-treated testes contained germ cells and round spermatids were detected in 14.2% of new tubules compared with 15.9% and 5.3% in testes not treated with ACV, respectively. At Day 150 the seminiferous epithelium was completely recovered in some donor tubules and elongated spermatids were observed inside it. Thus, our findings reveal the effectiveness of the combination of antiviral therapy with neonatal testis-cell transplantation for the restoration of spermatogenesis damaged by viral infection.

Infectious, inflammatory and ‘autoimmune’ male factor infertility: how do rodent models inform clinical practice?

“…5 and Table III ) ( Hedger, 2011a ; Satie et al , 2011 ). Animal models of viral infections of the male tract itself include mumps virus, cytomegalovirus and herpes simplex virus infections in mice ( Tebourbi et al , 2001 ; Malolina et al , 2016 ; Wu et al , 2016 ), Sendai virus infection in rats ( Melaine et al , 2003 ), Myxoma virus infection in rabbits ( Fountain et al , 1997 ) and simian immunodeficiency virus infection in monkeys ( Shehu-Xhilaga et al , 2005 ; Houzet et al , 2014 ; Winnall et al , 2015 ). In these various studies, infection was frequently associated with leucocytic infiltration (T cells, macrophages), an increase in local production of interferons and pro-inflammatory mediators, disruption of the seminiferous epithelium and primary Leydig cell failure with reduced testosterone levels.…”

The Role of Stem Cells and Their Derived Extracellular Vesicles in Restoring Female and Male Fertility

“…Orchitis usually occurs as a result of epididymitis that spreads to the surrounding tissues [ 220 ]. Inflammation of the male genital organ affects fertility through reduced germ and Sertoli cell numbers [ 221 ]. Increased intratesticular pressure as a result of inflammation damages the germinal epithelium [ 194 ].…”

“…However, Yeniyol et al found that systemic use of INF cannot completely prevent testicular atrophy [ 230 ]. Recently, the transplantation of neonatal testis-cells combined with the use of antiviral drugs was found to be effective in restoring testicular tissue of mice with herpes virus induced-orchitis [ 221 ].…”