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DETECTION OF A CRITICAL PERIOD NECESSARY FOR ATRAZINE-INDUCED MAMMARY GLAND DELAYS IN RATS
Citation:
Rayner, J. L. AND S E. Fenton. DETECTION OF A CRITICAL PERIOD NECESSARY FOR ATRAZINE-INDUCED MAMMARY GLAND DELAYS IN RATS. Presented at Triangle Consortium for Reproductive Biology, RTP, NC, February 07, 2004.
Description:
Detection of a Critical Period Necessary for Atrazine-Induced Mammary Gland Delays in Rats.
Jennifer L. Rayner1 and Suzanne E. Fenton2
1 University of North Carolina at Chapel Hill, DESE, Chapel Hill, NC, and 2 Reproductive Toxicology Division, USEPA, NHEERL/ORD, RTP, NC.
In utero exposure during gestational days (GD) 15-19 to 100 mg/kg atrazine (ATR) was shown to delay mammary gland (MG) development in the female offspring of Long Evans (LE) rats. To determine if there is a critical period of ATR exposure, dams were gestationally dosed at varying 3-day intervals and their offspring evaluated. Timed-pregnant LE rats (N= 8/group) were gavaged GD13-15, 15-17, 17-19, or 13-19 with 100 mg ATR/kg body weight (BW) or vehicle (controls, C) GD13-19. BW and MG development were compared on postnatal day (PND) 4, 22, 25, 33, and 46. No treatment effects on pup BW were detected at these times. MG whole-mounts were subjectively scored (2 scorers) for development (branching, lobules, end buds) and epithelial areas were measured (mm2). MG taken from GD15-17, 17-19, and 13-19 offspring (N>4dams/group, d/g) at PND4 displayed significant delays in epithelial development compared to C (p<0.002), and all exposed MG were smaller in area (p<0.001). At PND22 (N=3 d/g), MG taken from offspring in GD17-19 and 13-19 groups were developmentally delayed (p<0.009 vs. C), and areas were reduced in MG from those groups and GD15-17 (p<0.008). MG from animals in all groups were developmentally delayed at PND25 (N>5 d/g), 33 (N>6 d/g), and 46(N>4 d/g); p<0.05, p<0.0002, and p<0.0004 respectively, when compared to MG taken from C. Due to observed MG delays, we hypothesized that ATR-exposed animals may have difficulties in nursing their young. Females exposed in utero to either ATR (all groups as defined above) or C (N>3 in separate litters/group) were bred on PND68 and allowed to rear their offspring. Both female and male F2 fromGD17-19 and GD13-19 groups were significantly smaller in BW than those of C (p<0.0001, litter means, for both sexes) at PNDs 4 and 11, suggesting a need for further studies to clarify a possible adverse effect of ATR on MG development and function. (This abstract does not necessarily reflect EPA policy; Supported by NHEERL-DESE, EPA CT826513.)