title: Effects of male sexual maturity of reproductive endpoints relevant to DART studies in Wistar Hannover rats.
abstract: Wistar Hannover rats have been utilized as one of major strains in regulatory toxicology studies. This study was performed to verify the appropriate age of male sexual maturity in the development and reproductive toxicity (DART) study in Wistar Hannover rats (RccHan:WIST) by comparing reproductive endpoints between 8, 10 and 12 weeks of ages. Although fertility showed a tendency toward decrease in 8-week-old males, copulation index was not different among three ages. Testis weights reached a plateau at 10 weeks of age, whereas weights of other reproductive organs developed until 12 weeks of age. Indices of spermatogenesis (sperm motility, number of sperm in the epididymis and testis and contents of morphologically abnormal sperm) showed age-related progress and did not fully develop except for 12-week-old. For histology, epididymal tubules in 8-week-old animals showed immaturity with tall epithelium. At cesarean section, dams mated with 8-week-old males showed high incidence of preimplantation loss and the number of live fetuses was less than 10. In conclusion, although reproductive performance attained maturity by age of 10 weeks, spermatogenesis was not fully established at 10-week-old, which could result in a low fertility index. Therefore, we recommend that Wistar Hannover male rats at 12-week-old or older are used to conduct DART study properly and evaluate any adverse effects on dams and embryo-fetal development.
authors.affiliation: Safety Research Laboratory, R&D, Kissei Pharmaceuticals Co., Ltd.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Takakura
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Creasy
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yokoi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Terashima
authors.forename: Tomoya
authors.initials: T
authors.lastname: Onozato
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Chino
authors.forename: Toru
authors.initials: T
authors.lastname: Tahara
authors.forename: Toru
authors.initials: T
authors.lastname: Tamura
authors.forename: Junji
authors.initials: J
authors.lastname: Kuroda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kusama
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D005260:Female; D005298:Fertility / Q000502:physiology; D005837:Genitalia, Male / Q000254:growth & development*; D006801:Humans; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000502:physiology*; D012741:Sexual Maturation / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013091:Spermatogenesis / Q000502:physiology; D018675:Toxicity Tests; D014116:Toxicology / Q000379:methods*