Gestational and Chronic Low-Dose PFOA Exposures and Mammary Gland Growth and Differentiation in Three Generations of CD-1 Mice

National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
Environmental Health Perspectives (Impact Factor: 7.03). 04/2011; 119(8):1070-6. DOI: 10.1289/ehp.1002741
Source: PubMed

ABSTRACT Prenatal exposure to perfluorooctanoic acid (PFOA), a ubiquitous industrial surfactant, has been reported to delay mammary gland development in female mouse offspring (F1) and the treated lactating dam (P0) after gestational treatments at 3 and 5 mg PFOA/kg/day.
We investigated the consequences of gestational and chronic PFOA exposure on F1 lactational function and subsequent development of F2 offspring.
We treated P0 dams with 0, 1, or 5 mg PFOA/kg/day on gestation days 1-17. In addition, a second group of P0 dams treated with 0 or 1 mg/kg/day during gestation and their F1 and F2 offspring received continuous PFOA exposure (5 ppb) in drinking water. Resulting adult F1 females were bred to generate F2 offspring, whose development was monitored over postnatal days (PNDs) 1-63. F1 gland function was assessed on PND10 by timed-lactation experiments. Mammary tissue was isolated from P0, F1, and F2 females throughout the study and histologically assessed for age-appropriate development.
PFOA-exposed F1 dams exhibited diminished lactational morphology, although F1 maternal behavior and F2 offspring body weights were not significantly affected by P0 treatment. In addition to reduced gland development in F1 females under all exposures, F2 females with chronic low-dose drinking-water exposures exhibited visibly slowed mammary gland differentiation from weaning onward. F2 females derived from 5 mg/kg PFOA-treated P0 dams displayed gland morphology similar to F2 chronic water exposure groups on PNDs 22-63.
Gestational PFOA exposure induced delays in mammary gland development and/or lactational differentiation across three generations. Chronic, low-dose PFOA exposure in drinking water was also sufficient to alter mammary morphological development in mice, at concentrations approximating those found in contaminated human water supplies.


Available from: Suzanne Fenton, Jun 09, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: To examine associations between environmental exposure to perfluoroalkyl substances (PFASs) and ovarian hormone concentrations in naturally cycling women. E2 and P were measured in saliva samples collected daily for a single menstrual cycle and concentrations of PFASs (including perfluoroctane sulfonate [PFOS] and perfluoroctanoic acid) were measured in serum samples collected during the same cycle. Not applicable. A total of 178 healthy, naturally cycling women, aged 25-35 years. None. Mean follicular E2 (cycle days -7 to -1, where 0 is the day of ovulation); mean luteal P (cycle days +2 to 10). Among nulliparous, but not parous women, PFOS concentrations were inversely associated with E2 (β = -0.025, 95% CI -0.043, -0.007) and P (β = -0.027, 95% CI -0.048, -0.007). Similar, but weaker results were observed for perfluorooctanesulfonic acid. No associations were observed between other PFASs (including perfluoroctanoic acid) and ovarian steroid concentrations, nor were any associations noted in parous women. Our results demonstrate that PFOS and perfluorooctanesulfonic acid may be associated with decreased production of E2 and P in reproductive age women. These results suggest a possible mechanism by which PFASs affect women's health, and underscore the importance of parity in research on PFASs and women's reproductive health. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    Fertility and Sterility 03/2015; 103(5). DOI:10.1016/j.fertnstert.2015.02.001 · 4.30 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chemical exposures are in principle preventable causes of cancer. People are exposed to chemicals already during fetal period and the possibility of disturbances in human development by chemical compounds leading to cancer later in life has been proven by diethylstilbestrol. The mechanisms most probably include epigenetic modifications of promoter regions of key genes. The world-wide increases in cancer incidence and concurrent increase in the number and quantity of chemicals in the environment raises concerns about a link between these two. Developmental origin and related mechanisms in chemically induced human cancer are worth pursuing.
    Frontiers in Pharmacology 12/2011; 2:62. DOI:10.3389/fphar.2011.00062