title: 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 (P0) after gestational treatments at 3 and 5 mg PFOA/kg/day.
  
  
  OBJECTIVE
  We investigated the consequences of gestational and chronic PFOA exposure on F1 lactational function and subsequent development of F2 offspring.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Sally S
authors.initials: SS
authors.lastname: White
authors.forename: Jason P
authors.initials: JP
authors.lastname: Stanko
authors.forename: Kayoko
authors.initials: K
authors.lastname: Kato
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Calafat
authors.forename: Erin P
authors.initials: EP
authors.lastname: Hines
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Fenton
mesh_terms: D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D005865:Gestational Age; D007774:Lactation / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid