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PERSISTENT ABNORMALITIES IN THE RAT MAMMARY GLAND FOLLOWING GESTATIONAL AND LACTATIONAL EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)
Citation:
Fenton, S E., J. T. Hamm, L S. Birnbaum, AND G. L. Youngblood. PERSISTENT ABNORMALITIES IN THE RAT MAMMARY GLAND FOLLOWING GESTATIONAL AND LACTATIONAL EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD). TOXICOLOGICAL SCIENCES 67(1):63-74, (2002).
Description:
SUMMARY
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure during gestation has revealed reproductive anomalies in rat offspring, including inconclusive reports of stunted mammary development in females (Brown et al., 1998, Lewis et al., 2001). The current studies were designed to examine mammary gland development in female offspring exposed in utero and lactationally to TCDD, and determine a critical exposure period and cellular source of these effects. Long Evans rats were exposed to 1 ?g TCDD/kg body weight (BW) or vehicle on gestation day (GD)15. TCDD-exposed females sacrificed on postnatal days (PND) 4, 25, 33, 37, 45, and 68 weighed significantly less than control litter mates and peripubertal animals exhibited delayed vaginal opening and persistent vaginal threads, yet did not display altered estrus cyclicity. Mammary glands taken from TCDD-exposed animals on PND 4 demonstrated reduced primary branches, decreased epithelial elongation, and significantly fewer alveolar buds and lateral branches. This phenomenon persisted through PND 68 when, unlike fully developed glands of controls, TCDD-exposed rats retained undifferentiated terminal structures. Glands of offspring exposed to TCDD or oil on gestation days 15 and 20 or lactation days 1, 3, 5, and 10 were examined on PND 4 or 25 to discern that GD15 was a critical period that caused consistent inhibition of epithelial development. Experiments using mammary epithelial transplantation between control and TCDD-exposed females suggested that the stroma plays a major role in the retarded development of the mammary gland following TCDD exposure. Our data suggests that exposure to TCDD prior to migration of the mammary bud into the fat pad, permanently alters mammary epithelial development in female rat offspring.