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

White, Sally S ; Stanko, Jason P ; Kato, Kayoko ; Calafat, Antonia M ; Hines, Erin P ; Fenton, Suzanne E

Environmental Health Perspectives, 2011, Vol.119(8), p.1070-1076 [Peer Reviewed Journal]

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  • Title:
    Gestational and Chronic Low-Dose PFOA Exposures and Mammary Gland Growth and Differentiation in Three Generations of CD-1 Mice
  • Author/Creator: White, Sally S ; Stanko, Jason P ; Kato, Kayoko ; Calafat, Antonia M ; Hines, Erin P ; Fenton, Suzanne E
  • Subjects: Research ; Delayed Development ; Fetal Origins Of Adult Disease ; Lactation ; Mammary Gland ; Multigenerational ; Perfluorooctanoic Acid (Pfoa)
  • Is Part Of: Environmental Health Perspectives, 2011, Vol.119(8), p.1070-1076
  • Description: Background: Prenatal exposure to perfluorooctanoic acid (PFOA), a ubiquitous industrial surfactant, has been reported to delay mammary gland development in female mouse offspring (F 1 ) and the treated lactating dam (P 0 ) after gestational treatments at 3 and 5 mg PFOA/kg/day. Objective: We investigated the consequences of gestational and chronic PFOA exposure on F 1 lactational function and subsequent development of F 2 offspring. Methods: We treated P 0 dams with 0, 1, or 5 mg PFOA/kg/day on gestation days 1–17. In addition, a second group of P 0 dams treated with 0 or 1 mg/kg/day during gestation and their F 1 and F 2 offspring received continuous PFOA exposure (5 ppb) in drinking water. Resulting adult F 1 females were bred to generate F 2 offspring, whose development was monitored over postnatal days (PNDs) 1–63. F 1 gland function was assessed on PND10 by timed-lactation experiments. Mammary tissue was isolated from P 0 , F 1 , and F 2 females throughout the study and histologically assessed for age-appropriate development. Results: PFOA-exposed F 1 dams exhibited diminished lactational morphology, although F 1 maternal behavior and F 2 offspring body weights were not significantly affected by P 0 treatment. In addition to reduced gland development in F 1 females under all exposures, F 2 females with chronic low-dose drinking-water exposures exhibited visibly slowed mammary gland differentiation from weaning onward. F 2 females derived from 5 mg/kg PFOA-treated P 0 dams displayed gland morphology similar to F 2 chronic water exposure groups on PNDs 22–63. Conclusions: 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.
  • Identifier: ISSN: 0091-6765 ; E-ISSN: 1552-9924 ; DOI: 10.1289/ehp.1002741 ; PMCID: 3237341 ; PMID: 21501981