title: Gestational PFOA exposure of mice is associated with altered mammary gland development in dams and female offspring.
abstract: Perfluorooctanoic acid (PFOA), with diverse and widespread commercial and industrial applications, has been detected in human and wildlife sera. Previous mouse studies linked prenatal PFOA exposure to decreased neonatal body weights (BWs) and survival in a dose-dependent manner. To determine whether effects were linked to gestational time of exposure or to subsequent lactational changes, timed-pregnant CD-1 mice were orally dosed with 5 mg PFOA/kg on gestation days (GD) 1-17, 8-17, 12-17, or vehicle on GD 1-17. PFOA exposure had no effect on maternal weight gain or number of live pups born. Mean pup BWs on postnatal day (PND) 1 in all PFOA-exposed groups were significantly reduced and decrements persisted until weaning. Mammary glands from lactating dams and female pups on PND 10 and 20 were scored based on differentiation or developmental stages. A significant reduction in mammary differentiation among dams exposed GD 1-17 or 8-17 was evident on PND 10. On PND 20, delays in normal epithelial involution and alterations in milk protein gene expression were observed. All exposed female pups displayed stunted mammary epithelial branching and growth at PND 10 and 20. While control litters at PND 10 and 20 had average scores of 3.1 and 3.3, respectively, all treated litters had scores of 1.7 or less, with no progression of duct epithelial growth evident over time. BW was an insignificant covariate for these effects. These findings suggest that in addition to gestational exposure, abnormal lactational development of dams may play a role in early growth retardation of developmentally exposed offspring.
authors.affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Sally S
authors.initials: SS
authors.lastname: White
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Calafat
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Kuklenyik
authors.forename: LaTonya
authors.initials: L
authors.lastname: Villanueva
authors.forename: Robert D
authors.initials: RD
authors.lastname: Zehr
authors.forename: Laurence
authors.initials: L
authors.lastname: Helfant
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Strynar
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lindstrom
authors.forename: Julie R
authors.initials: JR
authors.lastname: Thibodeaux
authors.forename: Carmen
authors.initials: C
authors.lastname: Wood
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Fenton
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D005865:Gestational Age; D008099:Liver / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D018811:Maternal Exposure; D051379:Mice; D008894:Milk Proteins / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger; D013997:Time Factors
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D008894:Milk Proteins; D012333:RNA, Messenger; C023036:perfluorooctanoic acid