New method for detecting antiandrogenic effects through the measurement of external genitalia in rabbits.
The aim of the present study was to develop a quantitative evaluation method for detecting antiandrogenic activity of chemicals in rabbits that are regularly used for developmental toxicity studies. Kbl: New Zealand White rabbits (n = 8-9) were injected intramuscularly with an antiandrogen, cyproterone acetate (CA; 10 mg/kg body weight [BW]/day), on gestation days (GD) 13-24. On GD 29, live fetuses were obtained by cesarean section and sexed by examination of the internal genitalia. The external genitalia were evaluated in cross-section measurements of the phallus by both diameter and width of the ventral gap of the preputial lamella with a micrometer under a stereoscopic microscope. The diameters of the preputial lamella were 1015 +/- 83.5, 856 +/- 64.0, and 865 +/- 72.6 microm in control males, control females, and CA-treated males, respectively. The ventral gaps of the preputial lamella were 26 +/- 8.2, 437 +/- 72.3, and 318 +/- 59.4 microm in the control males, control females, and CA-treated males, respectively. There were statistically significant differences in both parameters between control males and control females or CA-treated males. The lower fetal BW in CA-treated males did not disturb the detection of the feminization of the ventral gap of the preputial lamella; however, the diameter of the preputial lamella might be influenced by fetal BW because no difference in the relative diameter of the preputial lamella was found between control males and CA-treated males. These results demonstrated that this approach could detect the antiandrogen activity of CA quantitatively by feminization of male external genitalia in rabbit fetuses.
Inawaka
Kunifumi
K
Sumitomo Chemical Co. Ltd, Osaka, Japan. inawaka@sc.sumitomo-chem.co.jp
Kishimoto
Noriyuki
N
Higuchi
Hashihiro
H
Okamoto
Takayuki
T
Kawamura
Satoshi
S
D000726:Androgen Antagonists / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D017373:Cyproterone Acetate / Q000494:pharmacology*; D005260:Female; D020567:Fetal Weight; D005333:Fetus / Q000187:drug effects; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011817:Rabbits
D000726:Androgen Antagonists; D017373:Cyproterone Acetate