title: Impairment of male fertility induced by muscarinic receptor antagonists in rats.
abstract: 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.
authors.affiliation: Safety Assessment, Banyu Pharmaceutical Co, Ltd, 810 Nishijo, Menuma-machi, Osato-gun, Saitama 360-0214, Japan. banyk@banyu.co.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Ban
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sato
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakatsuka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kemi
authors.forename: Keiji
authors.initials: K
authors.lastname: Samura
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Mark A
authors.initials: MA
authors.lastname: Cukierski
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: van Zwieten
mesh_terms: 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
chemical_list: D018727:Muscarinic Antagonists; D001285:Atropine