Impairment of male fertility induced by muscarinic receptor antagonists in rats.
Male rats were treated with a muscarinic receptor antagonist at 3, 10, and 100mg/kg/day for 4 weeks prior to mating with untreated females and their reproductive status was determined on gestation days (GD) 15-17. Treatment-related decreases in the pregnancy rate were observed at 100mg/kg/day without any effects on mating performance. Impairment of male fertility by this compound was also observed after treatment for 1 week, but there were no effects after a 1-week withdrawal period suggesting reversibility of the effect. There were no treatment-related effects on sperm production or motility, or testicular histopathology in any group. In order to determine whether the reduced fertility was a class effect of muscarinic receptor antagonists, atropine was examined. Males received atropine for 1 week at 62.5 and 125 mg/kg/day and were mated with untreated females. A low pregnancy rate associated with a decrease in the number of implantations was observed at 125 mg/kg/day. The effect on implantation was also observed at 62.5mg/kg/day. These findings suggest that the impairment of fertility in male rats induced by muscarinic receptor antagonists is a class effect, and has a relatively short onset of effect and is quickly reversible.
Ban
Yoshiki
Y
Safety Assessment, Banyu Pharmaceutical Co, Ltd, 810 Nishijo, Menuma-machi, Osato-gun, Saitama 360-0214, Japan. banyk@banyu.co.jp
Sato
Takahiro
T
Nakatsuka
Toshio
T
Kemi
Masayuki
M
Samura
Keiji
K
Matsumoto
Hiroyoshi
H
Cukierski
Mark A
MA
van Zwieten
Matthew J
MJ
D000284:Administration, Oral; D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D005298:Fertility / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D018873:Pregnancy Rate; D051381:Rats; D011919:Rats, Inbred Strains; D020127:Recovery of Function; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology
D018727:Muscarinic Antagonists; D001285:Atropine