Hypospadias and Incomplete Preputial Separation in Male Rats Induced by Prenatal Exposure to an Anti-androgen, Flutamide
| Autor: | Shinsuke Yoshimura, Noriko Ohsawa, Kazunori Konno, Akiko Chisaka, Satoshi Noguchi, Hajime Yamaguchi |
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| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | Journal of Toxicologic Pathology. 17:113-118 |
| ISSN: | 1881-915X 0914-9198 |
| Popis: | Hypospadias was induced in male Sprague-Dawley rats by prenatal exposure to 30 mg/kg/day of flutamide from gestational days 14 to 17, or from 18 to 21. Their external genitalia were examined histopathologically and compared to untreated controls. On postnatal day 6, the glans penis of untreated controls was bordered with epithelium. On postnatal day 22, papillae were recognized on the glans penis side, and cornification started close to the tip of the papilla on postnatal day 35. On postnatal day 42 cornification spread to the surface of the glans penis. The cornification progressed from tip to base of the glans penis, and from dorsal to ventral. When cornification reached the base of the glans penis, separation of the double layered epithelia was complete and the animal was considered sexually mature. Flutamide treatment on gestational days 14-17 induced a defect in the ventral half of the glans penis (cleft phallus) and cleft in the ventral prepuce (cleft prepuce) in the male pups, while treatment on gestational days 18-21 induced cleft phallus without apparent abnormalities in the prepuce. The external urethral orifice opened at the ventral end of the glans penis (hypospadias) in both treatment groups. In male pups with cleft phallus, cornification of the dorsal epithelium followed by separation of the prepuce occurred, while separation of the ventral part of glans penis did not occur because epithelium was not formed at the ventral part of the glans penis. Consequently, the onset of puberty was not decided in these animals. These findings indicate that the defect of the ventral half of the phallus is the reason why the time of sexual maturation was not decided, and that there is a difference between the phallus and prepuce in the sensitive period concerning the development of flutamide-induced malformations. |
| Databáze: | OpenAIRE |
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