Collaborative work to determine the optimal administration period and parameters to detect drug effects on male rat fertility--study on estradiol benzoate effects.
In order to examine the optimal administration period and parameters for male fertility assessment, male rats were subcutaneously administered 0.2, 2 or 20 micrograms/kg of estradiol benzoate (E2B), a known testicular toxicant, for 4 weeks or 9 weeks before mating. After 4 weeks administration, suppression of body weight gain and food consumption, decreases in prostate and seminal vesicle weights, atrophy of Leydig cells, and mature spermatid retention at stages IX, X and XI were observed in the 2 and 20 micrograms/kg groups. In the 20, micrograms/kg group, decreases in epididymides weight and copulation index were also found but the number of sperm and sperm motility were not affected. In the 0.2 micrograms/kg group, no changes were noted in any parameters. After 9 weeks administration, decreases in testis weight and the number and motility of sperm were observed in the 20, micrograms/kg group, in addition to the changes found after 4 weeks administration. These results suggest that detailed histopathological evaluation and determination of accessory sex organ weights are sensitive for evaluating the effects of E2B on male fertility. Results with the 4-weeks treatment were comparable to those with the 9-weeks treatment in terms of these parameters.
Ikegawa
S
S
Safety Research Department Pharmaceuticals Development Research Laboratories, Teijin Ltd., Tokyo, Japan.
Hata
J
J
Nakatomi
K
K
Asaga
H
H
Kaji
M
M
Sugawara
S
S
Uno
H
H
Izawa
Y
Y
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002585:Cesarean Section; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005837:Genitalia, Male / Q000187:drug effects / Q000473:pathology; D007248:Infertility, Male / Q000139:chemically induced* / Q000175:diagnosis*; D008136:Longevity / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000187:drug effects
C074283:estradiol 3-benzoate; D004958:Estradiol