title: Developmental exposure to xenoestrogens at low doses alters femur length and tensile strength in adult mice.
abstract: Developmental exposure to high doses of the synthetic xenoestrogen diethylstilbestrol (DES) has been reported to alter femur length and strength in adult mice. However, it is not known if developmental exposure to low, environmentally relevant doses of xenoestrogens alters adult bone geometry and strength. In this study we investigated the effects of developmental exposure to low doses of DES, bisphenol A (BPA), or ethinyl estradiol (EE(2)) on bone geometry and torsional strength. C57BL/6 mice were exposed to DES, 0.1 μg/kg/day, BPA, 10 μg/kg/day, EE(2), 0.01, 0.1, or 1.0 μg/kg/day, or vehicle from Gestation Day 11 to Postnatal Day 12 via a mini-osmotic pump in the dam. Developmental Xenoestrogen exposure altered femoral geometry and strength, assessed in adulthood by micro-computed tomography and torsional strength analysis, respectively. Low-dose EE(2), DES, or BPA increased adult femur length. Exposure to the highest dose of EE(2) did not alter femur length, resulting in a nonmonotonic dose response. Exposure to EE(2) and DES but not BPA decreased tensile strength. The combined effect of increased femur length and decreased tensile strength resulted in a trend toward decreased torsional ultimate strength and energy to failure. Taken together, these results suggest that exposure to developmental exposure to environmentally relevant levels of xenoestrogens may negatively impact bone length and strength in adulthood.
authors.affiliation: Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, Missouri, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Pelch
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Carleton
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Phillips
authors.forename: Susan C
authors.initials: SC
authors.lastname: Nagel
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D001696:Biomechanical Phenomena; D003094:Collagen / Q000378:metabolism; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000033:anatomy & histology* / Q000187:drug effects / Q000196:embryology*; D047109:Fetal Development / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D011247:Pregnancy; D013718:Tensile Strength / Q000187:drug effects*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003094:Collagen; D004054:Diethylstilbestrol; D004997:Ethinyl Estradiol; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
references.citation: Pediatr Res. 2007 Jan;61(1):48-53
references.pmid: 17211140
references.citation: J Clin Invest. 2006 Mar;116(3):561-70
references.pmid: 16511588
references.citation: Endocrinology. 1996 May;137(5):2118-25
references.pmid: 8612556
references.citation: Arch Biochem Biophys. 1961 May;93:440-7
references.pmid: 13786180
references.citation: Reprod Toxicol. 2002 Mar-Apr;16(2):117-22
references.pmid: 11955942
references.citation: Bone. 2003 Sep;33(3):387-98
references.pmid: 13678781
references.citation: Fertil Steril. 2004 Dec;82(6):1501-8
references.pmid: 15589850
references.citation: Environ Sci Technol. 2004 Oct 15;38(20):5476-83
references.pmid: 15543754
references.citation: Ann Intern Med. 1995 May 15;122(10):778-88
references.pmid: 7717601
references.citation: Environ Health Perspect. 2009 May;117(5):784-9
references.pmid: 19479022
references.citation: Environ Health Perspect. 1995 Oct;103 Suppl 7:95-7
references.pmid: 8593884
references.citation: Am J Obstet Gynecol. 1948 Nov;56(5):821-34
references.pmid: 18888213
references.citation: J Bone Miner Res. 1998 Nov;13(11):1648-56
references.pmid: 9797472
references.citation: Environ Health Perspect. 2010 Aug;118(8):1055-70
references.pmid: 20338858
references.citation: Med Sci Sports Exerc. 2000 May;32(5):911-7
references.pmid: 10795780
references.citation: J Toxicol Environ Health A. 2008;71(15):1032-42
references.pmid: 18569612
references.citation: Bone. 2000 Jul;27(1):47-52
references.pmid: 10865208
references.citation: Anal Bioanal Chem. 2010 Sep;398(1):571-6
references.pmid: 20623271
references.citation: Environ Health Perspect. 2008 Jan;116(1):39-44
references.pmid: 18197297
references.citation: J Bone Miner Res. 2010 Feb;25(2):190-9
references.pmid: 19594295
references.citation: Bone. 2008 Apr;42(4):681-94
references.pmid: 18313376
references.citation: Reprod Toxicol. 2007 Aug-Sep;24(2):139-77
references.pmid: 17825522
references.citation: J Bone Miner Metab. 2005;23 Suppl:16-22
references.pmid: 15984409
references.citation: Environ Toxicol. 2006 Apr;21(2):181-91
references.pmid: 16528694
references.citation: Reprod Toxicol. 2011 Jan;31(1):1-9
references.pmid: 20887781
references.citation: Cochrane Database Syst Rev. 2008 Oct 08;(4):CD003989
references.pmid: 18843653
references.citation: J Bone Miner Res. 1998 Jan;13(1):107-13
references.pmid: 9443796
references.citation: J Nutr. 2009 Mar;139(3):467-73
references.pmid: 19158220
references.citation: Endocrinology. 1992 Mar;130(3):1756-8
references.pmid: 1537323
references.citation: Chem Res Toxicol. 2001 Feb;14(2):149-57
references.pmid: 11258963
references.citation: Endocrinology. 1993 Jun;132(6):2279-86
references.pmid: 8504731
references.citation: Mech Dev. 1997 Jul;65(1-2):71-85
references.pmid: 9256346
references.citation: Lancet. 1993 Jan 9;341(8837):72-5
references.pmid: 8093403
references.citation: N Engl J Med. 1971 Apr 15;284(15):878-81
references.pmid: 5549830
references.citation: Endocrinology. 1997 Mar;138(3):863-70
references.pmid: 9048584
references.citation: Bone. 2008 Jul;43(1):110-118
references.pmid: 18467201
references.citation: Environ Health Perspect. 1995 Jun;103(6):608-12
references.pmid: 7556016
references.citation: Environ Health Perspect. 1996 Mar;104(3):298-305
references.pmid: 8919768
references.citation: Environ Sci Technol. 2002 Mar 15;36(6):1202-11
references.pmid: 11944670
references.citation: Anat Rec. 1996 Mar;244(3):416-22
references.pmid: 8742705
references.citation: J Bone Miner Res. 2005 May;20(5):809-16
references.pmid: 15824854
references.citation: Ann N Y Acad Sci. 2006 Apr;1068:429-46
references.pmid: 16831941
references.citation: Toxicol Sci. 2000 Mar;54(1):154-67
references.pmid: 10746942
references.citation: Bone. 2000 Aug;27(2):219-26
references.pmid: 10913914
references.citation: Lancet Oncol. 2007 Dec;8(12):1088-1100
references.pmid: 18054879
references.citation: Toxicology. 2005 Feb 14;207(2):215-21
references.pmid: 15596252
references.citation: Obstet Gynecol. 1978 Apr;51(4):453-8
references.pmid: 662228
references.citation: Mech Dev. 1999 Mar;81(1-2):163-7
references.pmid: 10330493
references.citation: Am Fam Physician. 1999 Nov 1;60(7):2073-84
references.pmid: 10569509
references.citation: Clin Chim Acta. 1967 Nov;18(2):267-73
references.pmid: 4864804
references.citation: Toxicol Lett. 2006 Dec 1;167(2):95-105
references.pmid: 17049190
references.citation: Environ Health Perspect. 2003 Jun;111(8):994-1006
references.pmid: 12826473
references.citation: Environ Health Perspect. 1993 Oct;101(5):378-84
references.pmid: 8080506
references.citation: Bone. 2002 Jul;31(1):8-11
references.pmid: 12110405
references.citation: Best Pract Res Clin Endocrinol Metab. 2006 Mar;20(1):35-43
references.pmid: 16522518