Disruption of the reproductive system and reproductive performance by administration of nonylphenol to newborn rats.
A number of alkylphenolic compounds are used in a variety of commercial products and have been shown in in vitro studies to be weakly estrogenic, but few in vivo data are available addressing this issue in mammals. Human exposure to alkylphenols may occur not only from these environmental contaminants but also through contact with manufactured and metabolic breakdown products. The reproductive function of rats treated subcutaneously with nonylphenol (NP, 500 mg/kg/day) or 17beta-estradiol (E2, 2 mg/kg/day) as a positive control, from postnatal days 1 to 5 was examined after puberty. In addition, masculine sexual behavior, sperm motion, plasma testosterone concentration and histopathological changes in the reproductive organs of the rats were examined. Furthermore, male rats were subjected to an open field test and wheel cage test to evaluate locomotor activity, and the estrous cycle was examined in female rats. All male and female rats exposed neonatally to NP or E2 showed macroscopic and/or microscopic alterations of the gonads. Females treated with NP or E2 showed an altered estrous cycle and abnormal reproductive function, while males treated with NP or E2 showed normal reproduction. In males exposed neonatally to NP or E2, no abnormalities were observed in locomotor activity, sperm motion or plasma testosterone concentration. The results of this study indicate that early neonatal exposure to NP causes dysfunction of postpubertal reproductive function in female rats, as well as disrupted development of gonads in male and female rats. More detailed studies are warranted to assess the possible risks to human and wildlife reproduction from exposure to NP and other environmental chemicals with estrogenic activity.
Department of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
T
T
Nagao
Y
Y
Saito
K
K
Usumi
M
M
Nakagomi
S
S
Yoshimura
H
H
Ono
D000818:Animals; D000831:Animals, Newborn; D004958:Estradiol / Q000008:administration & dosage / Q000633:toxicity; D004965:Estrogen Antagonists / Q000032:analysis / Q000633:toxicity*; D004971:Estrus / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D010053:Ovary / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013739:Testosterone / Q000097:blood; D018675:Toxicity Tests
D004965:Estrogen Antagonists; D010636:Phenols; D013739:Testosterone; D004958:Estradiol; C025256:nonylphenol