Collaborative work on evaluation of ovarian toxicity : 1) Effects of 2- or 4-week repeated-dose administration and fertility studies with medroxyprogesterone acetate in female rats
スポンサーリンク
概要
- 論文の詳細を見る
As a part of the collaborative study to evaluate the relationship between histopathological changes of the ovary and functional changes in female fertility, 2- and 4-week repeated-dose toxicity studies and a female fertility study were conducted using female Crl: CD (SD) rats using a synthetic progestagen of medroxyprogesterone acetate (MPA) as a test compound. MPA was administered to female rats by gavage at 0, 0.4, 2.0 and 10mg/kg/day for 2 and 4 weeks to assess the histopathological changes of ovaries and to pregnant rats at the same doses from 2 weeks prior to mating until day 7 of gestation to examine female fertility. The number of non-pregnant female rats with irregular estrous cycle increased in number and there was a decrease in weight of ovaries was observed at doses≥2.0mg/kg in the 2- and 4-week-treatment groups. The histopathological examination revealed an increased number of large atretic follicles and decreases in currently formed corpora lutea and previously-formed large or small ones were observed at the same doses in the 2- and 4-week treatment groups. In female fertility study, the number of animals with an irregular estrous cycle and elongation of mean estrous cycle increased at 0.4mg/kg, with no changes in fertility. A decreased number of copulating animals and a decreased gestation rate with low preimplantation loss were observed in the 2.0mg/kg-treatment group and no copulation was observed in the group treated with 10mg/kg. Based on these results, changes in fertility induced by MPA correlated well with histopathological changes of ovaries after 2 and 4 weeks of treatment, which suggests that a 2 weeks administration period is sufficient to detect ovarian toxicity of MPA with repeated dosing.
著者
-
Hisada Shigeru
Safety Research Department Developmental Research Center, ASKA Pharmaceutical Co., Ltd.
-
Hisada Shigeru
Safety Research Department Developmental Research Center Aska Pharmaceutical Co. Ltd.
-
Hisada Shigeru
Safety & Pharmacokinetics Research Department Teikoku Hormone Mfg. Co. Ltd.
-
OHTAKE Sachiyo
Safety & Pharmacokinetics Research Dep., Teikoku Hormone Mfg. Co., Ltd.
-
Fukui Motoko
Safety Research Department, Developmental Research Center, ASKA Pharmaceutical Co., Ltd.
-
Ootake Sachiyo
Safety Research Department Developmental Research Center Aska Pharmaceutical Co. Ltd.
-
Fukui Motoko
Safety Research Department Developmental Research Center Aska Pharmaceutical Co. Ltd.
関連論文
- Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats
- Morphological characterization of the ovary under normal cycling in rats and its viewpoints of ovarian toxicity detection
- Safety assessment of biopharmaceuticals : Japanese perspective on ICH S6 guideline maintenance
- W1-2 ICH Survey on Immunotoxicity Data(WORKSHOP 1: CURRENT OF ICH GUIDANCE ON IMMUNOTOXICITY TEST)(Proceedings of the 31st Annual Meeting)
- PD1-2 Role of histopathology in immunotoxicity evaluation(PANEL DISCUSSION 1: RECENT STATUS AND FUTURE PERSPECTIVES OF IMMUNOTOXICOLOGY)(Proceedings of the 31st Annual Meeting)
- Relationship between the accumulation of p53 protein and the level of DNA damage induced by ENNG and mitomycin C in human hepatoma HepG2 cells(Mutagenicity, Carcinogenicity, Proceedings of the 32nd Annual Meeting)
- O-21 An investigation of a possible method of genotoxic screening using RT-PCR analysis of p53-regulated genes(MUTAGENICITY)(GENERAL SESSION BY ORAL PRESENTATION)(Proceedings of the 31st Annual Meeting)
- Genotoxicity screening on an early phase of drug development using Ames miniscreen assay and in vitro micronucreus test (MUTAGENICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- Complete parallelism between enhancement of dopamine β -hydroxylase activity and increase in the rate of cell proliferation in adrenal medulla of male rats after reserpine treatment.
- Effects of in utero propylthiouracil exposure on the monoamine content of the rat fetus brain(Development, Reproduction, Proceedings of the 32nd Annual Meeting)
- Effects of the p38 MAP kinase inhibitor SB203580 on the immune system of rats(Immune system, Allergy, Proceedings of the 32nd Annual Meeting)
- Tissue distribution of rat plasma released enzymes(Blood, Proceedings of the 32nd Annual Meeting)
- P-66 Effects of Tamoxlfen Treatment on the Uterus and Ovary In Rats.(Proceedings of the 27th Annual Meeting)
- P-44 Some Consideration to the Significance of Serum Immunogiobulin Levels in the Immunotoxicy Testing(Proceedings of the 27th Annual Meeting)
- 22C-10-5 Differences in toxic changes between CB6F1-Tg-rasH2 mice and their nontransgenic littermates given cyclophosphamide by gavage weekly for 5 or 26 weeks (2) Immunotoxicity.
- 21D-03-1 Differences in toxic changes between CB6F1-Tg-rasH2 mice and their nontransgenic littermates given cyclophosphamide by gavage weekly for 5 or 26 weeks (1) General toxicity.
- Collaborative work on evaluation of ovarian toxicity : 1) Effects of 2- or 4-week repeated-dose administration and fertility studies with medroxyprogesterone acetate in female rats
- Spleen-Specific Development of Germinal Centers in Rats Treated with Antithyroid Drugs