title: Reproductive senescence, fertility and reproductive tumour profile in ageing female Han Wistar rats.
abstract: A study using vehicle administration in 104 female rats investigated reproductive aging in Han Wistar rats as a useful tool to interprete carcinogenicity studies where hormonal patterns are perturbated. From 16 weeks of age oestrous cycles were monitored every 6 weeks to investigate reproductive ageing. A subset of 20 females was used to assess fertility at 21 months of age. The animals were necropsied after 106-107 weeks on study and female reproductive organs, mammary glands and pituitary glands were examined for hyperplasias and/or tumours. The majority of rats had regular oestrous cycles up to 6 months of age. After this age, there was a rapid decline in the number of rats with regular oestrous cycles and an increase in irregular cycles and cycles in persistent di-oestrus with an occasional pro-oestrus. By the end of the study, the majority of animals were acyclic and the few remaining cyclic animals had irregular cycles. In the fertility assessment, 19/20 animals mated but only four animals became pregnant. These pregnant animals had normal numbers of corpora lutea of pregnancy but had high pre-implantation losses and could not sustain a viable pregnancy. 65 animals (62.5%) showed adenomas and/or pituitary hyperplasia in the pituitary gland at necropsy. The pituitary tumours were likely to be prolactin secreting that give rise to pseudopregnancy and mammary tumours, demonstrated by the fact that 43/65 (66%) of the affected animals had histopathological signs of these conditions. Multiple corpora lutea were found in 61% of all animals at time of termination. Only one uterine tumour was seen in this study probably due to lack of persistent oestrus seen in these animals.
authors.affiliation: Drug, Safety and Metabolism, AstraZeneca, AstraZeneca R&D Alderley, Alderley Park, Macclesfield SK10 4TG, England, UK. Electronic address: Terri.mitchard@astrazeneca.com.
authors.forename: Terri L
authors.initials: TL
authors.lastname: Mitchard
authors.affiliation: Drug, Safety and Metabolism, AstraZeneca, AstraZeneca R&D Alderley, Alderley Park, Macclesfield SK10 4TG, England, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Klein
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000502:physiology*; D005833:Genital Neoplasms, Female / Q000473:pathology*; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000473:pathology; D010911:Pituitary Neoplasms / Q000473:pathology; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000502:physiology*
keywords: Ageing; Fertility; Han Wistar; Rat; Reproductive senescence; Tumour profile