PMID- 29228316
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20190225
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 162
IP  - 2
DP  - 2018 Apr 1
TI  - Identification of a Critical Window for Ganciclovir-Induced Disruption of 
      Testicular Development in Rats.
PG  - 488-498
LID - 10.1093/toxsci/kfx276 [doi]
AB  - 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.
FAU - Meyer, Katlyn Barp
AU  - Meyer KB
AD  - Department of Physiology, Federal University of Parana, Curitiba, PR 81531-980, 
      Brazil.
FAU - Martino Andrade, Anderson Joel
AU  - Martino Andrade AJ
AD  - Department of Physiology, Federal University of Parana, Curitiba, PR 81531-980, 
      Brazil.
FAU - Venturelli, Amanda Caroline
AU  - Venturelli AC
AD  - Department of Physiology, Federal University of Parana, Curitiba, PR 81531-980, 
      Brazil.
FAU - Kita, Diogo Henrique
AU  - Kita DH
AD  - Department of Physiology, Federal University of Parana, Curitiba, PR 81531-980, 
      Brazil.
FAU - Machado, Daria Louise Barbosa
AU  - Machado DLB
AD  - Department of Physiology, Federal University of Parana, Curitiba, PR 81531-980, 
      Brazil.
FAU - Adams Philipsen, Rafaela
AU  - Adams Philipsen R
AD  - Department of Physiology, Federal University of Parana, Curitiba, PR 81531-980, 
      Brazil.
FAU - do Nascimento Silva, Alluanan Adelson
AU  - do Nascimento Silva AA
AD  - Department of Animal Morphology and Physiology, Federal Rural University of 
      Pernambuco, Recife, PE 52171900, Brazil.
FAU - Cantao, Isabelle
AU  - Cantao I
AD  - Department of Morphology and Genetics, Federal University of Sao Paulo, Sao 
      Paulo, SP 04023-900, Brazil.
FAU - Moreira, Davyson de Lima
AU  - Moreira DL
AD  - Natural Products Department, Institute of Pharmaceutical Technology - 
      Farmanguinhos, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ 21040-900, 
      Brazil.
FAU - da Silva Junior, Valdemiro Amaro
AU  - da Silva Junior VA
AD  - Department of Animal Morphology and Physiology, Federal Rural University of 
      Pernambuco, Recife, PE 52171900, Brazil.
FAU - Stumpp, Taiza
AU  - Stumpp T
AD  - Department of Morphology and Genetics, Federal University of Sao Paulo, Sao 
      Paulo, SP 04023-900, Brazil.
FAU - Morais, Rosana Nogueira
AU  - Morais RN
AD  - Department of Physiology, Federal University of Parana, Curitiba, PR 81531-980, 
      Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Antiviral Agents)
RN  - P9G3CKZ4P5 (Ganciclovir)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*administration & dosage/toxicity
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Ganciclovir/*administration & dosage/toxicity
MH  - Germ Cells/drug effects/pathology
MH  - Gestational Age
MH  - Male
MH  - Organogenesis/*drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/pathology
MH  - Rats
MH  - Rats, Wistar
MH  - Sexual Maturation/*drug effects
MH  - Testis/*drug effects/embryology/growth & development
MH  - Time Factors
EDAT- 2017/12/12 06:00
MHDA- 2019/02/26 06:00
CRDT- 2017/12/12 06:00
PHST- 2017/12/12 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
PHST- 2017/12/12 06:00 [entrez]
AID - 4706011 [pii]
AID - 10.1093/toxsci/kfx276 [doi]
PST - ppublish
SO  - Toxicol Sci. 2018 Apr 1;162(2):488-498. doi: 10.1093/toxsci/kfx276.