Establishment of a testicular germ cell tumor model in the Sprague-Dawley rat

• Grant number: 12/09873-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2012
• End date: May 06, 2015
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: João Lauro Viana de Camargo
• Grantee: Merielen Garcia Nascimento e Pontes
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Testicular germ cell tumors (TGCT) represent over 90% of testicular tumors in humans and its incidence has been increasing in several regions, including in Brazil. Its causes are not known, however, cryptorchidism occurs in 10% of cases of TGCT. The influence of environmental factors on the incidence of TGCT becomes increasingly evident. Special attention has been paid to endocrine disrupting substances such as acrylamide, and phthalates. Cyclophosphamide is a chemotherapic with recognized genotoxic activity to human's and rat's germ cells, this mode of action could be an useful tool in the study of testicular carcinogenesis. Since there is no validated experimental model for this neoplasia, the objective of this project is to establish such a model in Sprague-Dawley rats in order to assess the natural history of TGCTs. Pregnant rats will be alternately exposed to ciclofosfamida, DBP phthalate or acrylamide (5.0, 500.0 and 10.0 mg/kg/day, respectively) during the gestational periods (gavage) and lactation (diet). After surgical induction of cryptorchidism and orchidopexy the male offspring will continue to receive the chemical in the feed at the same concentrations as their progenitors for 10, 25 and 52 weeks. The animals will have evaluated the serum hormones profile (FSH, LH and ²-HCG), morphology of testis, prostate, seminal vesicles, pituitary, liver and testis immunohistochemistry for OCT3/4, DAZL, BrdU, caspase-3, PLAP, c-kit, vimentin and cytokeratin). Human seminoma cells in vitro, TCam-2, and germ cells from rats exposed to DBP for 25 and 52 weeks will be submitted to genomic profile analysis by qRT-PCR. This approach aims to determine whether rat's germ cells submitted to experimental protocol develops similar gene expression profile from seminoma. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE SOUZA, N. P.; FERRAGUT CARDOSO, A. P.; GOMIDE, L. M. M.; LIMA, T. R. R.; MIOT, H. A.; MARTINO-ANDRADE, A. J.; ARNOLD, L. L.; PENNINGTON, K. L.; COHEN, S. M.; DE CAMARGO, J. L. V.; et al. Experimental cryptorchidism enhances testicular susceptibility to dibutyl phthalate or acrylamide in Sprague-Dawley rats. HUMAN & EXPERIMENTAL TOXICOLOGY, v. 38, n. 8, p. 899-913, AUG 2019. (12/09873-4)

FERRAGUT CARDOSO, ANA P.; GOMIDE, LIGIA M. M.; SOUZA, NATHALIA P.; DE JESUS, CARLOS MARCIO N.; ARNOLD, LORA L.; COHEN, SAMUEL M.; DE CAMARGO, V, JOAO LAURO; NASCIMENTO E PONTES, MERIELEN G.. Time response of rat testicular alterations induced by cryptorchidism and orchiopexy. International Journal of Experimental Pathology, v. 102, n. 1, p. 57-69, FEB 2021. (12/09873-4)

LIMA, THANIA R. R.; SOUZA, NATHALIA P.; CARDOSO, ANA P. FERRAGUT; GOMIDE, LIGIA M. M.; PONTES, MERIELEN G. NASCIMENTO E; MIOT, HELIO A.; ARNOLD, LORA L.; COHEN, SAMUEL M.; DE CAMARGO, JOAO LAURO V.. Testicular alterations in cryptorchid/orchiopexic rats chronically exposed to acrylamide or di-butyl-phthalate. JOURNAL OF TOXICOLOGIC PATHOLOGY, v. 35, n. 2, p. 12-pg., 2022-01-01. (12/09873-4)