Effect of estradiol-filled polydimethylsiloxane subdermal implants in adult male rats on the reproductive system, fertility, and progeny outcome.
Combinations of testosterone and estradiol have been proposed as potential male contraceptives. For any compound to be an acceptable male contraceptive, it must be demonstrated either to prevent pregnancy completely or, if contraceptive failure occurs, to not have any adverse effect on pregnancy outcome. We have previously established that increasing doses of testosterone given via subdermal implants to adult male rats will decrease spermatogenesis and fertility but will not result in an increased incidence of pre- or postimplantation loss or in abnormal progeny. In the present study, we have monitored the effects of a dose of estradiol that has been proposed for the contraceptive regimen, as well as doses three and seven times as large, on progeny outcome. Adult male Sprague-Dawley rats received s.c. implants of estradiol-filled polydimethylsiloxane capsules of varying lengths and, after three months, were each mated twice to two females in proestrus. The smallest dose of estradiol (the dose used in the contraceptive formulation) did not have any significant effects on any of the measured parameters of the male reproductive system, or on the incidence of pre- or postimplantation loss or on progeny outcome. With increasing doses of estradiol, there was a marked reduction in fertility. This reduction in fertility was not associated with a sufficient decrease in epididymal sperm reserves to account for the decrease in number of females impregnated, but was associated with a major reduction in seminal plugs; this would suggest that the large doses of estradiol were decreasing male sexual behavior.(ABSTRACT TRUNCATED AT 250 WORDS)
Robaire
B
B
Centre for the Study of Reproduction, McGill University, Montreal, Quebec, Canada.
Duron
J
J
Hales
B F
BF
D000818:Animals; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005837:Genitalia, Male / Q000187:drug effects*; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome; D051381:Rats; D011919:Rats, Inbred Strains; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012833:Siloxanes; D013091:Spermatogenesis / Q000187:drug effects
D003692:Delayed-Action Preparations; D012833:Siloxanes; D004958:Estradiol