Reproductive effects in male and female rats of neonatal exposure to genistein.
Sprague-Dawley rats were administered genistein orally at doses of 12.5, 25, 50, or 100 mg/kg on postnatal days 1 through 5 to examine its effects on reproductive function after puberty. In addition, preputial separation and vaginal opening as endpoints of sexual maturation, estrous cycling, sperm count, serum testosterone concentration, and histopathologic changes of reproductive organs of male and female rats were examined. Body weights of male and female rats exposed to genistein at any dose level examined were lower than those of controls. Timing of preputial separation in males and timing of vaginal opening were not affected by genistein treatment. The number of females showing estrous cycle irregularities was increased by genistein treatment. The fertility of female rats exposed neonatally to genistein at 100 mg/kg was disrupted, while neonatal exposure to genistein did not affect male fertility. Neither sperm counts nor serum testosterone concentration were changed by neonatal exposure to genistein. Female rats exposed neonatally to genistein at 100 mg/kg showed histopathologic changes in the ovaries and uterus, while male rats showed no histopathologic alterations in the gonads. The results of this study indicate that early neonatal exposure to genistein caused dysfunction of postpubertal reproductive performance as well as abnormal development of gonads in female but not in male rats.
Nagao
T
T
Department of Reproductive and Developmental Biology, Hatano Research Institute, Food and Drug Safety Center, Hadano, Kanagawa, Japan. nagaot@kb3.so-net.ne.jp
Yoshimura
S
S
Saito
Y
Y
Nakagomi
M
M
Usumi
K
K
Ono
H
H
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004971:Estrus / Q000187:drug effects; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005298:Fertility / Q000187:drug effects*; D019833:Genistein / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D013739:Testosterone; D004997:Ethinyl Estradiol; D019833:Genistein