Perinatal ethinyl oestradiol alters mammary gland development in male and female Wistar rats.
ABSTRACT Increased attention is being paid to human mammary gland development because of concerns for environmental influences on puberty onset and breast cancer development. Studies in rodents have showed a variety of changes in the mammary glands after perinatal exposure to endocrine disrupting chemicals, indicating progressed development of mammary glands when exposed to oestrogens early in life. However, laboratories use different parameters to evaluate the development of mammary glands, making studies difficult to compare. Moreover, studies of whole mounts in Wistar rats are lacking. In the present study, Wistar rats were exposed to 0, 5, 15 or 50 μg/kg of ethinyl oestradiol per day during gestation and lactation. A wide range of morphological parameters were evaluated in whole mounts of mammary glands from male and female offspring PD21-22. This study showed that in both male and female pre-pubertal Wistar rats, mammary gland development was accelerated after perinatal oestrogen exposure with increase in size, density and number of terminal end buds (TEBs). In female rats, the most sensitive parameters were the distance to the fifth gland, the relative growth towards the lymph node and the overall density. The sensitive endpoints in male rats were TEB numbers, both in the whole gland and in the zone C, the overall- and the highest density. The overall density was sensitive in both male and female rats and was considered a good representative of both branching and budding of the gland. The number of TEBs in zone C was representative of the number of TEBs in the whole gland. Further studies in older Wistar rats and with weak oestrogenic compounds could be performed to validate mammary gland examination as an endpoint in reproductive toxicity studies and to examine how early life environmental exposures may alter mammary gland development, disrupt lactation and alter susceptibility to breast cancer.
- SourceAvailable from: nih.gov[show abstract] [hide abstract]
ABSTRACT: A case-control study was conducted in Los Angeles County, California, of 163 very young breast-cancer cases (all aged 32 or less at diagnosis) to investigate the role, if any, of oral contraceptives (OC) in the development of the disease. OC use before first full-term pregnancy (FFTP) was associated with an elevated risk, which increased with duration of OC use (relative risk approximately 2.2 at 6 years of use, P < 0.01). This increased risk could not be explained by other risk factors. OC use after FFTP was not associated with any change in risk. A first-trimester abortion before FFTP, whether spontaneous or induced, was associated with a 2.4-fold increase in breast-cancer risk (P < 0.005).British Journal of Cancer 02/1981; 43(1):72-6. · 5.08 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Bisphenol A (BPA), known as an environmental endocrine disruptor, is widely used as a plasticizer. This study aims to investigate whether exposure in utero to BPA alters the architecture, proliferative index, and genomic signature of the rat mammary gland during critical stages of development. Pregnant rats were gavaged with 25 microg BPA/kg body weight (BW; low-dose group) or 250 microg BPA/kg BW (high-dose group) from day 10 post-conception to delivery. Female litters were euthanized at 21, 35, 50, and 100 days, and mammary glands were collected. Analysis of gland morphology was performed from whole-mounted mammary tissue, while proliferative index was determined by detection of bromodeoxyuridine incorporation in the epithelial cells. Genomic profiles were obtained by microarray analysis, and some genes were validated by real-time RT-PCR. BPA exposure induced changes in the mammary gland that were time and dose specific. High-dose exposure resulted in architectural modifications, mainly in the number of undifferentiated epithelial structures of the breast tissue. Proliferative index did not show remarkable differences by the effect of BPA. Low and high doses of BPA changed the gene expression signature of the mammary gland following a different fashion: low dose had the highest effect by 50 days, while high dose had a highest influence on gene expression by 100 days. Both doses presented a significant cluster of up-modulated genes related to the immune system at the age of maximal changes. Moreover, high-dose exposure induced changes in genes related to differentiation suggesting alterations in the normal development of the gland. The increase of undifferentiated structures and the changes in the gene expression profile at different ages suggest that prenatal exposure to BPA can affect the susceptibility of the mammary gland to transformation.Journal of Endocrinology 02/2008; 196(1):101-12. · 4.06 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Male breast cancer is rare, and little is known about state population-level patterns of incidence. The primary objective of this study was to determine the incidence of MBC in Florida in comparison with the Surveillance, Epidemiology, and End RESULTS (SEER) program data. Study data were obtained from the Florida Cancer Data System (FCDS). All males with pathologically confirmed invasive breast carcinoma diagnosed from 1985 to 2000 were included. Age-adjusted incidence rates, regional incidence rates, and descriptive statistics were calculated. Annual percent change (APC) for the study period was calculated with a linear model. Results were compared with the SEER data. A total of 1396 cases of MBC were identified. Age-adjusted incidence rates increased from 0.9 cases per 100,000 in 1990 to 1.5 cases per 100,000 in 2000. In 2000, the highest rates were in the age groups of 70 to 75 years (7.9) and > or =85 years (12.5). Infiltrating ductal was the most common subtype (92%); less common subtypes included mucinous (2%) and papillary (2%). Localized disease accounted for 45% of all cases, with regional disease in 33%, distant metastases in 7%, and unstaged in 15%. Most incident cases were diagnosed in the Palm Beach-Broward region (23%). The number of cases increased from 56 in 1985 to 132 new cases in 2000. The APC for this 16-year period was 2.0% (95% confidence interval [CI], 1.05-3.01; P <.005). SEER data indicated no change in MBC incidence rates (APC, 0.5; NS). The incidence of MBC in Florida increased significantly between 1985 and 2000. This finding is discordant with SEER incidence data. Further epidemiologic studies are warranted to investigate regional variation.Annals of Surgical Oncology 09/2004; 11(8):751-5. · 4.12 Impact Factor