Identification of a Critical Window for Ganciclovir-Induced Disruption of Testicular Development in Rats

Identification of a Critical Window for Ganciclovir-Induced Disruption of Testicular Development in Rats

Author Meyer, Katlyn Barp Google Scholar
Andrade, Anderson Joel Martino Google Scholar
Venturelli, Amanda Caroline Google Scholar
Kita, Diogo Henrique Google Scholar
Machado, Daria Louise Barbosa Google Scholar
Philipsen, Rafaela Adams Google Scholar
Silva, Alluanan Adelson do Nascimento Google Scholar
Cantao, Isabelle Hernandez Autor UNIFESP Google Scholar
Moreira, Davyson de Lima Google Scholar
Silva, Valdemiro Amaro da Google Scholar
Stumpp, Taiza Autor UNIFESP Google Scholar
Morais, Rosana Nogueira Google Scholar
Abstract Ganciclovir (GCV) has been implicated in the development of testicular alterations. Exposure on gestational day (GD) 10 in rats induced permanent effects, including focal reduction or absence of germ cells (Sertoli cell-only tubules). Because the timing of exposure can be critical for testicular effects, we exposed rat dams to 300 mg/kg GCV (3 100 mg/kg subcutaneous injections) on GD10, 14 and 19, when germ cells have high rates of migration, proliferation and are mitotically quiescent, respectively. Males exposed to GCV in utero on GD10 and 14 were evaluated for androgenization markers, serum and fecal androgens, and testicular histomorphometry at adulthood. Double-labeling immunofluorescence for DAZL and Ki67 were used to assess gonocytes number and the proliferative activity of germ and somatic cells in fetal testes on GD15 and 20, ie, 24 h after GCV exposure. Adult rats exposed on GD14 showed delayed puberty onset, despite normal androgen levels. Also, there was a 50% reduction in testicular weight and about 30% of seminiferous tubules lacking germ cells. Effects on GD10 animals were less pronounced. In the fetal testis, the number of gonocytes was reduced by 50% in rats exposed on GD14, but normal in GD19 fetuses. GCV also reduced Sertoli cell proliferation immunolabeling in GD19 fetuses and Sertoli cell number in adults. In conclusion, GCV toxicity on germ cells seems to be linked to their proliferation rate and GD14 is a critical window in rats, when GCV exposure causes an acute massive loss of germ cells that persists until adulthood.
Keywords fetal development
gonadal function
rodents
primordial germ cells
testis
toxicology
xmlui.dri2xhtml.METS-1.0.item-coverage Oxford
Language English
Sponsor Coordination for Enhancement of Higher Education Personnel (CAPES
PROAP)
CAPES (REUNI)
Date 2018
Published in Toxicological Sciences. Oxford, v. 162, n. 2, p. 488-498, 2018.
ISSN 1096-6080 (Sherpa/Romeo, impact factor)
Publisher Oxford Univ Press
Extent 488-498
Origin http://dx.doi.org/10.1093/toxsci/kfx276
Access rights Closed access
Type Article
Web of Science ID WOS:000429021100015
URI https://repositorio.unifesp.br/handle/11600/55747

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