Testicular effects following in utero exposure to the antivirals acyclovir and ganciclovir in rats.
In utero exposure to the antivirals acyclovir and ganciclovir has been reported to induce gross structural defects in rat offspring. The present study investigated the effects of maternal antiviral treatment on gestation day 10 on reproductive and nonreproductive organs in male rat offspring with a particular focus on the testes. Vehicle and two doses of acyclovir and ganciclovir, 75 and 300 mg/kg, were administered to rat dams. The total doses were fractioned into three subcutaneous applications (3 × distilled water, 3 × 25 mg/kg, and 3 × 100 mg/kg) that were administered on gestation day 10 at 8:00 a.m., 1:00 p.m., and 6:00 p.m. The antiviral concentrations were measured in the serum of the dams 1 h after the last administration. Exposure to 300 mg/kg ganciclovir induced germ cell deficiency in both fetal and adult testes, an effect that was not seen in any other treatment group. Adult rats exposed in utero to this high ganciclovir dose exhibited Sertoli cell-only tubules intermingled with seminiferous tubules that displayed a normal size and normal cell counts, alterations that resemble focal Sertoli cell-only syndrome in humans. The serum concentrations of ganciclovir were markedly higher than those of acyclovir, particularly at the high dose tested. However, although 300 mg/kg acyclovir did not induce germ cell deficiency, other specific effects were seen in exposed animals, including incomplete eye opening and reduced thymus weight.
Departamento de Fisiologia, Universidade Federal do Paraná, Centro Politécnico, Curitiba 81531-980, Brazil.
Fabíola
F
Nihi
Davyson
D
Moreira
Ana Carolina
AC
Santos Lourenço
Caroline
C
Gomes
Samanta Luiza
SL
Araujo
Renata Mercer
RM
Zaia
Natalia Botelho
NB
Trevisani
Leonardo
L
de Athayde Pinto
Daniele Dietrich
DD
Moura-Costa
Rosana Nogueira
RN
de Morais
Francisco José
FJ
Roma Paumgartten
Anderson Joel
AJ
Martino-Andrade
D000212:Acyclovir / Q000633:toxicity*; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D005260:Female; D015774:Ganciclovir / Q000633:toxicity*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D051381:Rats; D013737:Testis / Q000187:drug effects*
D000998:Antiviral Agents; D015774:Ganciclovir; D000212:Acyclovir
acyclovir; ganciclovir; gestation; rats; testis