title: Programming of metabolic effects in C57BL/6JxFVB mice by in utero and lactational exposure to perfluorooctanoic acid.
abstract: Perfluorooctanoic acid (PFOA) is known to cause developmental toxicity and is a suggested endocrine disrupting compound (EDC). Early life exposure to EDCs has been implicated in programming of the developing organism for chronic diseases later in life. Here we study perinatal metabolic programming by PFOA using an experimental design relevant for human exposure. C57BL/6JxFVB hybrid mice were exposed during gestation and lactation via maternal feed to seven low doses of PFOA at and below the NOAEL used for current risk assessment (3-3000 µg/kg body weight/day). After weaning, offspring were followed for 23-25 weeks without further exposure. Offspring showed a dose-dependent decrease in body weight from postnatal day 4 to adulthood. Growth under high fat diet in the last 4-6 weeks of follow-up was increased in male and decreased in female offspring. Both sexes showed increased liver weights, hepatic foci of cellular alterations and nuclear dysmorphology. In females, reductions in perigonadal and perirenal fat pad weights, serum triglycerides and cholesterol were also observed. Endocrine parameters, such as glucose tolerance, serum insulin and leptin, were not affected. In conclusion, our study with perinatal exposure to PFOA in mice produced metabolic effects in adult offspring. This is most likely due to disrupted programming of metabolic homeostasis, but the assayed endpoints did not provide a mechanistic explanation. The BMDL of the programming effects in our study is below the current point of departure used for calculation of the tolerable daily intake.
authors.affiliation: Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA, Bilthoven, The Netherlands.|Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
authors.forename: J C J
authors.initials: JC
authors.lastname: van Esterik
authors.affiliation: Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Bastos Sales
authors.affiliation: Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA, Bilthoven, The Netherlands.
authors.forename: M E T
authors.initials: ME
authors.lastname: Dollé
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, SE-171 77, Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Håkansson
authors.affiliation: Institute of Environmental Medicine, Karolinska Institutet, P.O. Box 210, SE-171 77, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Herlin
authors.affiliation: Department of Chemistry and Biology, Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Legler
authors.affiliation: Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA, Bilthoven, The Netherlands. Leo.van.der.ven@RIVM.nl.
authors.forename: L T M
authors.initials: LT
authors.lastname: van der Ven
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000008:administration & dosage / Q000633:toxicity*; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid; D002784:Cholesterol
keywords: Developmental exposure; Endocrine disrupting compounds; Metabolic effects; Perfluorooctanoic acid; Programming
references.citation: Toxicol Sci. 2010 May;115(1):214-24
references.pmid: 20118188
references.citation: Nutr Rev. 2013 Oct;71 Suppl 1:S88-94
references.pmid: 24147929
references.citation: Toxicology. 2007 Sep 24;239(1-2):15-33
references.pmid: 17681415
references.citation: Toxicol Pathol. 2010 Dec;38(7 Suppl):5S-81S
references.pmid: 21191096
references.citation: Environ Sci Technol. 2007 Jun 1;41(11):3891-7
references.pmid: 17612165
references.citation: Arch Toxicol. 2012 Sep;86(9):1349-67
references.pmid: 22456834
references.citation: Int J Androl. 2008 Apr;31(2):161-9
references.pmid: 18315716
references.citation: JAMA. 2012 Jan 25;307(4):391-7
references.pmid: 22274686
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Reprod Toxicol. 2009 Jun;27(3-4):212-230
references.pmid: 19429401
references.citation: Neurotox Res. 2011 Apr;19(3):452-61
references.pmid: 20512442
references.citation: Reprod Toxicol. 2012 Jul;33(4):491-505
references.pmid: 22154759
references.citation: Environ Health Perspect. 2008 Mar;116(3):322-8
references.pmid: 18335098
references.citation: Environ Res. 2014 Jul;132:62-9
references.pmid: 24742729
references.citation: Toxicol Sci. 2007 Jun;97(2):595-613
references.pmid: 17383973
references.citation: Int J Obes (Lond). 2010 Oct;34 Suppl 1:S23-7
references.pmid: 20935661
references.citation: Toxicol Sci. 2007 Feb;95(2):452-61
references.pmid: 17093205
references.citation: Chemosphere. 2013 May;91(8):1099-106
references.pmid: 23399300
references.citation: Toxicology. 2014 Jul 3;321:40-52
references.pmid: 24726836
references.citation: Reprod Toxicol. 2012 Jul;33(4):506-512
references.pmid: 22146484
references.citation: Lancet. 1998 Jan 17;351(9097):173-7
references.pmid: 9449872
references.citation: Am J Clin Nutr. 2011 Apr;93(4):897S-900
references.pmid: 21289222
references.citation: Environ Sci Technol. 2008 Feb 15;42(4):995-1003
references.pmid: 18351063
references.citation: Biochem Pharmacol. 2003 Sep 1;66(5):749-56
references.pmid: 12948855
references.citation: Reprod Toxicol. 2009 Jun;27(3-4):299-306
references.pmid: 19013232
references.citation: EFSA J. 2008 Jul 21;6(7):653
references.pmid: 37213838
references.citation: Environ Health Perspect. 2014 Oct;122(10):1040-51
references.pmid: 24968389
references.citation: Mol Cell Endocrinol. 2009 May 25;304(1-2):97-105
references.pmid: 19433254
references.citation: Reprod Toxicol. 2009 Jun;27(3-4):289-298
references.pmid: 19095057
references.citation: Environ Health Perspect. 2011 Aug;119(8):1070-6
references.pmid: 21501981
references.citation: Neurotoxicology. 2008 Jan;29(1):160-9
references.pmid: 18063051
references.citation: Environ Health Perspect. 2012 May;120(5):668-73
references.pmid: 22306490
references.citation: Environ Health Perspect. 2007 Nov;115(11):1596-602
references.pmid: 18007991
references.citation: Environ Int. 2013 Sep;59:112-23
references.pmid: 23792420
references.citation: Environ Health Perspect. 2009 Apr;117(4):660-7
references.pmid: 19440508
references.citation: Int J Environ Res Public Health. 2014 Jul 10;11(7):7001-21
references.pmid: 25014249
references.citation: Toxicol Sci. 2011 Jul;122(1):134-45
references.pmid: 21482639
references.citation: Toxicol Sci. 2002 Apr;66(2):298-312
references.pmid: 11896297
references.citation: Toxicol Sci. 2007 Feb;95(2):462-73
references.pmid: 17098816
references.citation: Nat Genet. 2003 Sep;35(1):49-56
references.pmid: 12910269
references.citation: Pathobiol Aging Age Relat Dis. 2011;1:
references.pmid: 22953029
references.citation: Toxicol Sci. 2006 Apr;90(2):510-8
references.pmid: 16415327
references.citation: Environ Health Perspect. 2007 Nov;115(11):1677-82
references.pmid: 18008003
references.citation: Reprod Toxicol. 2012 Jul;33(4):563-576
references.pmid: 22414604
references.citation: Environ Health. 2013 Apr 19;12(1):35
references.pmid: 23597293
references.citation: Environ Health Perspect. 2012 Oct;120(10):1432-7
references.pmid: 22935244
references.citation: Epigenetics. 2010 Aug 16;5(6):539-46
references.pmid: 20523118
references.citation: Environ Sci Pollut Res Int. 2013 Nov;20(11):8031-44
references.pmid: 23764977
references.citation: Environ Health Perspect. 2007 Nov;115(11):1670-6
references.pmid: 18008002
references.citation: J Expo Sci Environ Epidemiol. 2010 Nov;20(7):589-97
references.pmid: 19865074
references.citation: Environ Sci Technol. 2006 Jan 1;40(1):32-44
references.pmid: 16433330
references.citation: Toxicol Sci. 2007 Mar;96(1):133-44
references.pmid: 17132714
references.citation: J Steroid Biochem Mol Biol. 2011 Oct;127(1-2):16-26
references.pmid: 21397692
references.citation: J Altern Complement Med. 2002 Apr;8(2):185-92
references.pmid: 12006126