Gestational and chronic low-dose PFOA exposures and mammary gland Growth and differentiation in three generations of CD-1 mice

Abstract

Background: 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 (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.