COLLABORATIVE PROJECT TO ESTABLISH THE OPTIMAL PERIOD AND PARAMETERS FOR DETECTION OF REPRODUCTIVE TOXICITY IN MALE RATS - EFFECTS OF COMPOUND T ON MALE FERTILITY -

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Author(s)

    • OOSHIMA Yojiro
    • Drug Safety Research Laboratories, Hikari Branch, Pharmaceutical Development Division, Takeda Chemical Industries, Ltd.
    • CHATANI Fumio
    • Drug Safety Research Laboratories, Hikari Branch, Pharmaceutical Development Division, Takeda Chemical Industries, Ltd.
    • SUGITANI Toshiyasu
    • Drug Safety Research Laboratories, Hikari Branch, Pharmaceutical Development Division, Takeda Chemical Industries, Ltd.
    • TANAKAMARU Zen-yo
    • Drug Safety Research Laboratories, Hikari Branch, Pharmaceutical Development Division, Takeda Chemical Industries, Ltd.
    • FUJI Jun-ichiro
    • Drug Safety Research Laboratories, Hikari Branch, Pharmaceutical Development Division, Takeda Chemical Industries, Ltd.

Abstract

To assess the optimal dosing period and parameters for measurement of effects on male fertility, Compound T was administered to male Jcl : Wistar rats at dosage levels of 0, 2, 10 and/or 50 mg/kg/day for 4 weeks (Experiment 1) or for 9 weeks (Experiment 2). Experiment 1 : In the 50 mg/kg group, the ventral prostate weight was low when compared to the control value, and desquamation of round spermatids was observed in the tested. Experiment 2 : when treated males were mated with untreated females after dosing for 9 weeks (the first mating), the fertility index was slightly lowered and pre-implantation loss was significantly elevated in the 50 mg/kg group as compared to the control values. In this treatment group, serum testosterone level at 2.5 hours after dosing was significantly decreased after dosing for 12 weeks, and degeneration of spermatids/spermatocytes in the testis and epididymis was observed after dosing for 13 weeks. After a recovery period of for 6 weeks, remating resulted in copulatory and fertility indices and cesarean section data which were comparable in all groups. In conclusion, there were no differences in toxicity relevant to male fertility between 4 and 9 weeks of dosing, and it is considered that the observed changes resulted from decreased function of Sertoli cells due to depressed production/secretion of testosterone.

Journal

  • The Journal of Toxicological Sciences

    The Journal of Toxicological Sciences 20(3), 229-238, 1995-08

    The Japanese Society of Toxicology

References:  11

Cited by:  1

Codes

  • NII Article ID (NAID)
    110001805732
  • NII NACSIS-CAT ID (NCID)
    AN00002808
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    03881350
  • Data Source
    CJP  CJPref  NII-ELS  J-STAGE 
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