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

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 post natal 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.