OBJECTIVES: To investigate influence for the testicular development and to assess the usefulness as an animal model, cryptorchid rats were induced by exposure to flutamide during the fetal period and their testes examined histologically. METHODS: Flutamide was injected into the abdomen of pregnant rats for 7 days from the 14th to 20th day of gestation. The male offspring in which cryptorchidism was observed at 28 days after birth were defined as the model rats. They were divided into four groups by dosage of flutamide (2.5 mg, 5 mg, 7.5 mg, 15 mg per day), and their testicular weight, spermatogenesis (modified Johnsen score), and germ cell apoptosis were examined histochemically at 10 weeks after birth. RESULTS: The incidence of cryptorchidism including both unilateral and bilateral in the 2.5, 5, 7.5 and 15-mg flutamide groups was 58.3%, 81.9%, 93.6% and 91.0%, respectively. In the model rats, the undescended testes were located at the caudal end of the abdominal cavity, and these testes weighed less than the contra-descended testes in each group. Histologically, apoptotic cells were markedly increased, the seminiferous tubules were degenerated and disturbance of spermatid differentiation was observed in the undescended testes compared with the normal or contra-lateral descended testes. CONCLUSIONS: We found out that the incidence of undescended testes increased in a flutamide dose-dependent manner. The findings of histological examination were independent of the administrated dose of flutamide and it is suggested that exposure of the testes to abdominal temperature causes spermatogenic arrest with germ cell apoptosis. The present animal model indicates high incidence of above 90%, has no surgical stress and dose not require special techniques. We believe that the present model is a useful tool for the understanding of pathogenesis and treatment of cryptorchidism and further biological research into spermatogenesis.
OBJECTIVES: To investigate influence for the testicular development and to assess the usefulness as an animal model, cryptorchid rats were induced by exposure to flutamide during the fetal period and their testes examined histologically. METHODS:Flutamide was injected into the abdomen of pregnant rats for 7 days from the 14th to 20th day of gestation. The male offspring in which cryptorchidism was observed at 28 days after birth were defined as the model rats. They were divided into four groups by dosage of flutamide (2.5 mg, 5 mg, 7.5 mg, 15 mg per day), and their testicular weight, spermatogenesis (modified Johnsen score), and germ cell apoptosis were examined histochemically at 10 weeks after birth. RESULTS: The incidence of cryptorchidism including both unilateral and bilateral in the 2.5, 5, 7.5 and 15-mg flutamide groups was 58.3%, 81.9%, 93.6% and 91.0%, respectively. In the model rats, the undescended testes were located at the caudal end of the abdominal cavity, and these testes weighed less than the contra-descended testes in each group. Histologically, apoptotic cells were markedly increased, the seminiferous tubules were degenerated and disturbance of spermatid differentiation was observed in the undescended testes compared with the normal or contra-lateral descended testes. CONCLUSIONS: We found out that the incidence of undescended testes increased in a flutamide dose-dependent manner. The findings of histological examination were independent of the administrated dose of flutamide and it is suggested that exposure of the testes to abdominal temperature causes spermatogenic arrest with germ cell apoptosis. The present animal model indicates high incidence of above 90%, has no surgical stress and dose not require special techniques. We believe that the present model is a useful tool for the understanding of pathogenesis and treatment of cryptorchidism and further biological research into spermatogenesis.
Authors: Jason K Gurney; Katherine A McGlynn; James Stanley; Tony Merriman; Virginia Signal; Caroline Shaw; Richard Edwards; Lorenzo Richiardi; John Hutson; Diana Sarfati Journal: Nat Rev Urol Date: 2017-06-27 Impact factor: 14.432
Authors: Nadia Ferlazzo; Antonio Micali; Herbert Ryan Marini; Josè Freni; Giuseppe Santoro; Domenico Puzzolo; Francesco Squadrito; Giovanni Pallio; Michele Navarra; Santa Cirmi; Letteria Minutoli Journal: Pharmaceuticals (Basel) Date: 2021-04-21
Authors: Pietro Antonuccio; Herbert Ryan Marini; Antonio Micali; Carmelo Romeo; Roberta Granese; Annalisa Retto; Antonia Martino; Salvatore Benvenga; Salvatore Cuzzocrea; Daniela Impellizzeri; Rosanna Di Paola; Roberta Fusco; Raimondo Maximilian Cervellione; Letteria Minutoli Journal: Nutrients Date: 2021-02-25 Impact factor: 5.717
Authors: Pietro Antonuccio; Antonio Micali; Domenico Puzzolo; Carmelo Romeo; Giovanna Vermiglio; Violetta Squadrito; Jose Freni; Giovanni Pallio; Vincenzo Trichilo; Maria Righi; Natasha Irrera; Domenica Altavilla; Francesco Squadrito; Herbert R Marini; Letteria Minutoli Journal: Nutrients Date: 2020-05-25 Impact factor: 5.717