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 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.