Lack of maternal dietary exposure effects of bisphenol A and nonylphenol during the critical period for brain sexual differentiation on the reproductive/endocrine systems in later life.
Two potential endocrine-disrupting chemicals, bisphenol A (BPA) and nonylphenol (NP), were assessed for their long-lasting effects on endocrine/reproductive systems following transplacental and lactational exposure to rat offspring during a time-window that included the critical period for brain sexual differentiation. Each chemical was mixed with diet at concentrations of 60, 600 and 3000 ppm and was provided to maternal Sprague-Dawley rats from gestational day (GD) 15 to postnatal day (PND) 10. Ethinylestradiol (EE) at 0.5 ppm was used as an estrogenic reference drug. During pregnancy and lactation, including the exposure period, a soy-free rodent diet was provided to eliminate possible modification of the study results by plant-derived phytoestrogens. Effects on endocrine/reproductive systems were evaluated by examining the anogenital distance, organ weights before puberty, onset of puberty, estrous cyclicity, and organ weights and histopathology of adult endocrine organs (at 11 weeks of age), as well as the volume of the sexually dimorphic nucleus of preoptic area. Both NP and BPA, at high doses, caused decreases in maternal body weights and retardation of offspring growth, but neither affected any of the endocrine/reproductive endpoints of offspring, whereas EE induced irreversible changes in estrous cyclicity and histopathology of ovaries and uterus of adult females. The results indicated that maternal dietary exposure to NP or BPA at concentrations up to 3000 ppm from GD 15 through PND 10 do not exert any apparent adverse effects on the endocrine/reproductive systems of offspring.
Takagi
Hironori
H
Division of Pathology, National Institute of Health Sciences, 158-8501, Tokyo, Japan.
Shibutani
Makoto
M
Masutomi
Naoya
N
Uneyama
Chikako
C
Takahashi
Noriyuki
N
Mitsumori
Kunitoshi
K
Hirose
Masao
M
D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004703:Endocrine System / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005835:Genitalia / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D007774:Lactation; D018811:Maternal Exposure / Q000009:adverse effects*; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013997:Time Factors; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D010636:Phenols; C025256:nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds