Cyclophosphamide in the seminal fluid of treated males: Transmission to females by mating and effect on pregnancy outcome

Abstract

Cyclophosphamide is an anticancer and immunosuppressant drug administered to men of reproductive age. In the present study the ability of cyclophosphamide and/or its metabolites to enter secretions of the male reproductive tract, to be transmitted to the female partner upon mating, and to alter progeny outcome was assessed. [ 14C]Cyclophosphamide was given intravenously to adult male Sprague-Dawley rats; radiolabel (greater than 96% cyclophosphamide) was first found in seminal vesicle fluid within 10 min and equilibrated with plasma radioactivity within 30 min. Furthermore, radiolabel from cyclophosphamide given to the male was transmitted to the female upon mating up to 5 hr post-drug treatment. To study possible consequences of paternal treatment with cyclophosphamide on pregnancy outcome, male rats were administered a single dose of cyclophosphamide, 10, 30, or 100 mg/kg, or saline immediately prior to cohabitation with females in proestrus. There was no effect on the number of pregnant females per sperm-positive females but there was a significant decrease in the number of implantations per pregnant female per male and in the number of live fetuses per pregnant female per male. There was a twofold increase in preimplantation loss. There was no increase in postimplantation loss or number of abnormal fetuses. These results demonstrate that cyclophosphamide not only penetrates the male reproductive tract but that it can be transmitted to the female partner and can affect progeny outcome.