Jennifer L. Rayner - Doctoral Dissertation Final Defense

The herbicide atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine, ATR) is used to control growth of broadleaf and grassy weeds. It has been registered with the Environmental Protection Agency and is monitored to prevent unsafe levels of this possible endocrine disrupting compound from reaching human and animal populations via contaminated surface or ground water. Life-time feeding studies on ATR have shown an increased incidence and decreased time to tumors in mammary gland (MG) of rats, via its effects on the brain and altered estrous cyclicity. This work focuses on changes observed in developing MG of female Long Evans rats (offspring and dam) exposed during late gestation to ATR. It also explores possible confounders of observed effects including body weights, pubertal timing, and serum hormone concentrations.

Dams were gavage dosed with 100 mg/kg ATR during late gestation corresponding to fetal mammary bud development and outgrowth. That exposure caused a delay in puberty and mammary development in female offspring. From cross-fostered litters, it was determined that nursing from an ATR-treated dam delayed both puberty and mammary development. However, a brief transplacental exposure to ATR caused delays only in MG development that persist into adulthood. MG development was most delayed in offspring exposed during fetal mammary epithelial cell proliferation (GD17-19), but it was also delayed in offspring exposed only by nursing from dams treated during that same time. These results suggested that ATR may reprogram fetal and neonatal MG development.

These findings suggested changes in dam MG development or lactation. MG from dams exposed to ATR were developmentally different from those of controls at early timepoints. ATR and its metabolites were also found in the urine, amniotic fluid, and serum of treated dams at several timepoints post exposure suggesting that ATR metabolites may be available to the developing offspring until at least PND11 when abnormal MG development has been detected in female pups. These studies taken together suggest that ATR can have long-term effects of the MG of female offspring and dams without association of confounders. The effects of this brief exposure are persistent, extending into adulthood and affecting weight gain via the lactational effects in future generations.

Committee Members
Dr. Louise M. Ball (chair)
Dr. Suzanne E. Fenton
Dr. Noelle Granger
Dr. Sid Hunter
Dr. Li You

For further information please contact Rebecca Riggsbee Lloyd by email at Rebecca_Lloyd@unc.edu