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NONYLPHENOL AND ATRAZINE INDUCE INVERSE EFFECTS ON MAMMARY GLAND DEVELOPMENT IN FEMALE RATS EXPOSED IN UTERO
Citation:
Moon, H. J., C. R. Davis, AND S E. Fenton. NONYLPHENOL AND ATRAZINE INDUCE INVERSE EFFECTS ON MAMMARY GLAND DEVELOPMENT IN FEMALE RATS EXPOSED IN UTERO. Presented at Society of Toxicology, Nashville, TN, March 17-21, 2002.
Description:
Nonylphenol and Atrazine Induce Inverse Effects on Mammary Gland Development in Female Rats Exposed In Utero.
HJ Moon1, SY Han1, CC Davis2, and SE Fenton2
1 Department of Toxicology, NITR, Korea FDA, 5Nokbun-Dong, Eunpyung-Gu, Seoul, Korea and 2 Reproductive Toxicology Division, MD-72 NHEERL, ORD, USEPA, RTP, NC.
These experiments tested whether exposure to 4-nonylphenol (NP) or atrazine (ATR) during fetal mammary bud outgrowth alters mammary gland (MG) development in adult female offspring. Time pregnant Long Evans rats (N=7-8/treatment) were gavaged with NP (10 or 100 mg/kg), ATR (100 mg/kg), or corn oil on gestation days (GD) 15-19. MGs from female pups were removed and prepared as whole mounts or histological sections on postnatal days (PND) 4, 22, 33 and 41. Delayed MG development was detected on PND4 in ATR pups, and persisted through PND41(stunted epithelial progression through the fat pad, fewer primary and lateral branches). High dose NP pups had advanced lobular development of their MG by PND22 (in contrast, in controls at PND41). Low dose NP glands were not morphologically different from controls. Immunohistochemical comparisons of mammary sections from PND 41 demonstrated low levels of estrogen receptor (ER) staining in control gland stroma and epithelium, and was visibly increased in tissue of pups exposed to NP and ATR. ATR also elevated ER in the stroma surrounding the terminal end buds (TEB). Progesterone receptor (PR) staining was visibly decreased in the epithelium of NP100 glands vs. control glands. However, PR was present at high levels in epithelium of NP10 glands and was even more prominent in ATR-exposed ductal epithelium and fat cell nuclei. PR was expressed in TEB of all rats, but was undetectable in the TEB cap cell layer. Prolactin staining was elevated vs. control levels only in glands containing lobule areas (NP-exposed). These qualitative evaluations suggest that the environmental contaminants, NP and ATR, have opposite effects on MG development following gestational exposure. These exposures during a critical period of epithelial outgrowth altered levels of mammary PR and prolactin, which may contribute to the differences in mammary morphology at PND41. (This abstract has been reviewed in accordance with USEPA policy and approved for publication)