Neonatal testicular cell transplantation restores murine spermatogenesis damaged in the course of herpes simplex virus-induced orchitis.
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.
Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, Gamaleya str. 16, 123098, Moscow, The Russian Federation.
Ekaterina A
EA
Malolina
Kol'tsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilova str. 26, 119071, Moscow, The Russian Federation.
Andrey Yu
AY
Kulibin
Ivanovsky Institute of Virology, Ministry of Health of the Russian Federation, Gamaleya str. 16, 123098, Moscow, The Russian Federation.
Alla A
AA
Kushch
D000212:Acyclovir / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D017690:Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D003131:Combined Modality Therapy / Q000009:adverse effects; D006558:Herpes Genitalis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D007150:Immunohistochemistry; D007248:Infertility, Male / Q000209:etiology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D007700:Kinetics; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009920:Orchitis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D012671:Seminiferous Tubules / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012708:Sertoli Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018139:Simplexvirus / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification; D013087:Spermatids / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
D000998:Antiviral Agents; D000212:Acyclovir