A 40-week male fertility study of the anticancer agent sulofenur (LY186641) administered orally to rats.
Sulofenur was evaluated for fertility effects on rats. Five-week old male rats (20/group) received 0, 5, 30, or 60 mg Sulofenur/kg/day for 14 weeks. Fertility was evaluated five times. Treated males were mated with untreated females at 10 weeks. Half the males from each group were necropsied after the 14-week treatment period and the remainder were mated four additional times during a 26-week posttreatment period. Following each mating, females were killed on gestation-day 20 and examined for evidence of pregnancy. Six weeks after mating trial 5, the remaining males were necropsied. Testes and epididymides were collected, weighed, and examined microscopically. All rats mated in each mating trial, and all control and low-dose animals were fertile. A significant reduction in fertility occurred in the middle- and high-dose males. This was consistent with testicular hypospermatogenesis in these groups. Fertility recovered in the high-dose group following cessation of treatment, but remained reduced in the middle-dose group. Preimplantation and postimplantation loss in mating trial 1 were higher in the middle- and high-dose groups. Abnormal fetuses were present in the high-dose group in mating trial 3, but not in mating trials 4 or 5. In conclusion, male rats given doses of 30 and 60 mg/kg/day of Sulofenur showed hypospermatogenesis and decreased fertility. Spermatogenesis and fertility recovered in the high-dose group. A dose of 5 mg/kg/day did not produce any effect on testes or fertility.
Seyler
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Toxicology Research Laboratories, Lilly Research Laboratories, Greenfield, IN 46140.
Cochrane
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Todd
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GC
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005328:Fetal Viability / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013091:Spermatogenesis / Q000187:drug effects*; D013453:Sulfonylurea Compounds / Q000633:toxicity*; D013737:Testis / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D014599:Uterus / Q000187:drug effects
D000970:Antineoplastic Agents; D013453:Sulfonylurea Compounds; C058179:sulofenur