Abstract 2931: Exposure of rat dams to a high-fat or estradiol-supplemented diet during pregnancy alters mammary gland morphology and increases mammary cancer risk in their daughters and granddaughters

Abstract

Abstract It has been proposed that the risk of some chronic diseases in adulthood, including breast cancer, is influenced by exposures acting in early development, possibly beyond a single generation. We previously showed that feeding mothers a high fat (n-6 PUFA) diet during pregnancy increases pregnancy estradiol levels and the risk of mammary cancer in the female offspring. In this study we aimed to investigate whether exposing pregnant rats to a high fat or estrogen-supplemented diet would affect the risk of mammary cancer not only in their daughters but also in the granddaughters. Pregnant rat dams were divided in three groups and fed the following diets during gestation: 1) AIN93G control diet (17% energy from fat), 2) estradiol-supplemented diet (E2, 0.1ppm) or 3) high fat diet (HF, 43 % energy from fat). Once they delivered, all dams were switched to the AIN93G control diet. Pups were weaned at PND 21 and, at this time, 6 female rats/group were sacrificed for mammary tissue collection. Remaining F1 females were mated 5 weeks later with males from the same group to produce the F2 generation. All F1 pregnant dams were fed AIN93G control diet for the extent of pregnancy. The F2 generation was weaned at PND 21 and 6 female rats/group were sacrificed for tissue collection. Mammary gland whole-mounts of both F1 and F2 generation were processed and the number of TEBs was counted under a light microscope. We then investigated whether morphological changes observed in the mammary gland correlated with mammary tumorigenesis in the F1 and F2 generations. Mammary tumors were induced by exposing F1 and F2 generations female rats to 7,12-dimethylbenz[a]anthracene (DMBA) on PND 50. Tumorigenesis was monitored for 20 weeks. The number of terminal end buds was increased in the mammary glands of daughters (F1) of rats fed an HF or E2 diets during pregnancy (p=0.004). Importantly, the number of TEBs was also increased in the mammary gland of the granddaughters (F2) of rats fed an E2 or a HF diet during pregnancy (p=0.018). In the F1 generation, mammary tumorigenesis was higher in the E2 and HF groups compared to controls, as previously shown (mammary tumor incidence (p=0.022), tumor multiplicity (p=0.021) and total tumor burden (p<0.001) vs. control). In the F2 generation, mammary tumor incidence was significantly higher than in the HF group compared to the control group (p=0.037). In the E2 (F2) group, the tumor monitoring has not yet been completed. This study provides critical evidence that what mothers are exposed to during pregnancy, not only affects her offspring's mammary cancer risk, also affects the mammary cancer risk of the subsequent generation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2931.