Endocrine disruption of vitamin D activity by perfluoro-octanoic acid (PFOA).
Adolescent
Caprylates
/ pharmacology
Cell Line, Tumor
Cross-Sectional Studies
Endocrine Disruptors
/ pharmacology
Fluorocarbons
/ pharmacology
Humans
Male
Molecular Docking Simulation
Molecular Dynamics Simulation
Osteoblasts
/ drug effects
Parathyroid Hormone
/ blood
Receptors, Calcitriol
/ metabolism
Vitamin D
/ blood
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 10 2020
08 10 2020
Historique:
received:
12
05
2020
accepted:
14
09
2020
entrez:
9
10
2020
pubmed:
10
10
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Perfluoroalkyl substances (PFAS) are a class of compounds used in industry and consumer products. Perfluorooctanoic acid (PFOA) is the predominant form in human samples and has been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity, and immunotoxicity. Toxicological studies indicate that PFAS accumulate in bone tissues and cause altered bone development. Epidemiological studies have reported an inverse relationship between PFAS and bone health, however the associated mechanisms are still unexplored. Here, we present computational, in silico and in vitro evidence supporting the interference of PFOA on vitamin D (VD). First, PFOA competes with calcitriol on the same binding site of the VD receptor, leading to an alteration of the structural flexibility and a 10% reduction by surface plasmon resonance analysis. Second, this interference leads to an altered response of VD-responsive genes in two cellular targets of this hormone, osteoblasts and epithelial cells of the colorectal tract. Third, mineralization in human osteoblasts is reduced upon coincubation of PFOA with VD. Finally, in a small cohort of young healthy men, PTH levels were higher in the exposed group, but VD levels were comparable. Altogether these results provide the first evidence of endocrine disruption by PFOA on VD pathway by competition on its receptor and subsequent inhibition of VD-responsive genes in target cells.
Identifiants
pubmed: 33033332
doi: 10.1038/s41598-020-74026-8
pii: 10.1038/s41598-020-74026-8
pmc: PMC7545187
doi:
Substances chimiques
Caprylates
0
Endocrine Disruptors
0
Fluorocarbons
0
Parathyroid Hormone
0
Receptors, Calcitriol
0
Vitamin D
1406-16-2
perfluorooctanoic acid
947VD76D3L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16789Références
Conder, J. M., Hoke, R. A., De Wolf, W., Russell, M. H. & Buck, R. C. Are PFCAs bioaccumulative? A critical review and comparison with regulatory criteria and persistent lipophilic compounds. Environ. Sci. Technol. 42, 995–1003 (2008).
pubmed: 18351063
doi: 10.1021/es070895g
Foresta, C., Tescari, S. & Di Nisio, A. Impact of perfluorochemicals on human health and reproduction: a male’s perspective. J. Endocrinol. Invest. 41, 639–645 (2018).
pubmed: 29147953
doi: 10.1007/s40618-017-0790-z
pmcid: 29147953
Lau, C. et al. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicol. Sci. 99, 366–394 (2007).
pubmed: 17519394
doi: 10.1093/toxsci/kfm128
Geiger, S. D. et al. The association between PFOA, PFOS and serum lipid levels in adolescents. Chemosphere 98, 78–83 (2014).
pubmed: 24238303
doi: 10.1016/j.chemosphere.2013.10.005
pmcid: 24238303
Lin, C. Y., Chen, P. C., Lin, Y. C. & Lin, L. Y. Association among serum perfluoroalkyl chemicals, glucose homeostasis, and metabolic syndrome in adolescents and adults. Diabetes Care 32, 702–707 (2009).
pubmed: 19114613
doi: 10.2337/dc08-1816
pmcid: 19114613
Nelson, J. W., Hatch, E. E. & Webster, T. F. Exposure to polyfluoroalkyl chemicals and cholesterol, body weight, and insulin resistance in the general U.S. population. Environ. Health Perspect. 118, 197–202 (2010).
pubmed: 20123614
doi: 10.1289/ehp.0901165
Martinsson, M. et al. Intrauterine exposure to perfluorinated compounds and overweight at age 4: A case-control study. PLoS ONE 15, e0230137 (2020).
pubmed: 32176721
pmcid: 7075550
doi: 10.1371/journal.pone.0230137
Liu, H. S., Wen, L. L., Chu, P. L. & Lin, C. Y. Association among total serum isomers of perfluorinated chemicals, glucose homeostasis, lipid profiles, serum protein and metabolic syndrome in adults: NHANES, 2013–2014. Environ. Pollut. 232, 73–79 (2018).
pubmed: 28923343
doi: 10.1016/j.envpol.2017.09.019
Qi, W., Clark, J. M., Timme-Laragy, A. R. & Park, Y. Perfluorobutanesulfonic acid (PFBS) potentiates adipogenesis of 3T3-L1 adipocytes. Food Chem. Toxicol. 120, 340–345 (2018).
pubmed: 30031040
pmcid: 6169790
doi: 10.1016/j.fct.2018.07.031
Koskela, A. et al. Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation. Toxicol. Appl. Pharmacol. 301, 14–21 (2016).
pubmed: 27068293
doi: 10.1016/j.taap.2016.04.002
pmcid: 27068293
Bogdanska, J. et al. Tissue distribution of 35S-labelled perfluorooctane sulfonate in adult mice after oral exposure to a low environmentally relevant dose or a high experimental dose. Toxicology 284, 54–62 (2011).
pubmed: 21459123
doi: 10.1016/j.tox.2011.03.014
pmcid: 21459123
Pérez, F. et al. Accumulation of perfluoroalkyl substances in human tissues. Environ. Int. 59, 354–362 (2013).
pubmed: 23892228
doi: 10.1016/j.envint.2013.06.004
pmcid: 23892228
Koskela, A. et al. Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation. Sci. Rep. 7, 6841 (2017).
pubmed: 28754927
pmcid: 5533791
doi: 10.1038/s41598-017-07359-6
Lin, L. Y., Wen, L. L., Su, T. C., Chen, P. C. & Lin, C. Y. Negative association between serum perfluorooctane sulfate concentration and bone mineral density in US premenopausal women: NHANES, 2005–2008. J. Clin. Endocrinol. Metab. 99, 2173–2180 (2014).
pubmed: 24606077
doi: 10.1210/jc.2013-3409
pmcid: 24606077
Khalil, N. et al. Association of perfluoroalkyl substances, bone mineral density, and osteoporosis in the U.S. population in NHANES 2009–2010. Environ. Health Perspect. 124, 81–87 (2016).
pubmed: 26058082
doi: 10.1289/ehp.1307909
pmcid: 26058082
Khalil, N. et al. Perfluoroalkyl substances, bone density, and cardio-metabolic risk factors in obese 8–12 year old children: a pilot study. Environ. Res. 160, 314–321 (2018).
pubmed: 29040951
doi: 10.1016/j.envres.2017.10.014
pmcid: 29040951
Jeddy, Z. et al. Prenatal concentrations of perfluoroalkyl substances and bone health in British girls at age 17. Arch. Osteoporos. 13, 84 (2018).
pubmed: 30076472
pmcid: 6093196
doi: 10.1007/s11657-018-0498-5
Di Nisio, A. et al. Perfluoroalkyl substances and bone health in young men: a pilot study. Endocrine 67, 678–684 (2020).
pubmed: 31565782
doi: 10.1007/s12020-019-02096-4
pmcid: 31565782
Hu, Y. et al. Perfluoroalkyl substances and changes in bone mineral density: a prospective analysis in the POUNDS-LOST study. Environ. Res. 179, 108775 (2019).
pubmed: 31593837
doi: 10.1016/j.envres.2019.108775
pmcid: 31593837
Lopez-Espinosa, M.-J., Mondal, D., Armstrong, B. G., Eskenazi, B. & Fletcher, T. Perfluoroalkyl substances, sex hormones, and insulin-like growth factor-1 at 6–9 years of age: a cross-sectional analysis within the c8 health project. Environ. Health Perspect. 124, 1269–1275 (2016).
pubmed: 26794451
pmcid: 4977043
doi: 10.1289/ehp.1509869
Di Nisio, A. et al. Endocrine disruption of androgenic activity by perfluoroalkyl substances: clinical and experimental evidence. J. Clin. Endocrinol. Metab. 104, 1259–1271 (2019).
pubmed: 30403786
doi: 10.1210/jc.2018-01855
Ballesteros, V. et al. Exposure to perfluoroalkyl substances and thyroid function in pregnant women and children: a systematic review of epidemiologic studies. Environ. Int. 99, 15–28 (2017).
pubmed: 27884404
doi: 10.1016/j.envint.2016.10.015
Lee, J. E. & Choi, K. Perfluoroalkyl substances exposure and thyroid hormones in humans: epidemiological observations and implications. Ann. Pediatr. Endocrinol. Metab. 22, 6 (2017).
pubmed: 28443254
pmcid: 5401824
doi: 10.6065/apem.2017.22.1.6
Lewis, R. C., Johns, L. E. & Meeker, J. D. Serum biomarkers of exposure to perfluoroalkyl substances in relation to serum testosterone and measures of thyroid function among adults and adolescents from NHANES 2011–2012. Int. J. Environ. Res. Public Health 12, 6098–6114 (2015).
pubmed: 26035660
pmcid: 4483690
doi: 10.3390/ijerph120606098
Battault, S. et al. Vitamin D metabolism, functions and needs: from science to health claims. Eur. J. Nutr. 52, 429–441 (2013).
pubmed: 22886046
doi: 10.1007/s00394-012-0430-5
Lips, P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr. Rev. 22, 477–501 (2001).
pubmed: 11493580
doi: 10.1210/edrv.22.4.0437
Tsiaras, W. G. & Weinstock, M. A. Factors influencing vitamin d status. Acta Dermato-Venereologica 91, 115–124 (2011).
pubmed: 21384086
doi: 10.2340/00015555-0980
Johns, L. E., Ferguson, K. K. & Meeker, J. D. Relationships between urinary phthalate metabolite and bisphenol a concentrations and Vitamin D Levels in U.S. Adults: National health and nutrition examination survey (NHANES), 2005–2010. J. Clin. Endocrinol. Metab. 101, 4062–4069 (2016).
pubmed: 27648964
pmcid: 5095248
doi: 10.1210/jc.2016-2134
Johns, L. E. et al. Urinary BPA and phthalate metabolite concentrations and plasma vitamin D levels in pregnant women: a repeated measures analysis. Environ. Health Perspect. 125, 087026 (2017).
pubmed: 28934718
pmcid: 5783673
doi: 10.1289/EHP1178
Benninghoff, A. D. et al. Estrogen-like activity of perfluoroalkyl acids in vivo and interaction with human and rainbow trout estrogen receptors in vitro. Toxicol. Sci. 120, 42 (2011).
pubmed: 21163906
doi: 10.1093/toxsci/kfq379
Gao, Y., Li, X. & Guo, L. H. Assessment of estrogenic activity of perfluoroalkyl acids based on ligand-induced conformation state of human estrogen receptor. Environ. Sci. Technol. 47, 634 (2013).
pubmed: 23214429
doi: 10.1021/es304030x
pmcid: 23214429
Goudarzi, H. et al. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: the Hokkaido study. Environ. Health Perspect. 125, 111–118 (2017).
pubmed: 27219028
doi: 10.1289/EHP142
Zhao, Y., Tan, Y. S., Haslam, S. Z. & Yang, C. Perfluorooctanoic acid effects on steroid hormone and growth factor levels mediate stimulation of peripubertal mammary gland development in C57BL/6 mice. Toxicol. Sci. 115, 214–224 (2010).
pubmed: 20118188
pmcid: 2855353
doi: 10.1093/toxsci/kfq030
Etzel, T. M., Braun, J. M. & Buckley, J. P. Associations of serum perfluoroalkyl substance and vitamin D biomarker concentrations in NHANES, 2003–2010. Int. J. Hyg. Environ. Health 222, 262–269 (2019).
pubmed: 30503928
doi: 10.1016/j.ijheh.2018.11.003
Ciesielski, F., Rochel, N. & Moras, D. Adaptability of the vitamin d nuclear receptor to the synthetic ligand gemini: remodelling the lbp with one side chain rotation. J. Steroid Biochem. Mol. Biol. 103, 235–242 (2007).
pubmed: 17218092
doi: 10.1016/j.jsbmb.2006.12.003
pmcid: 17218092
Fleet, J. C. & Wood, R. J. Identification of calbindin d-9k mrna and its regulation by 1,25-dihydroxyvitamin d3 in caco-2 cells. Arch. Biochem. Biophys. 308, 171–174 (1994).
pubmed: 8311449
doi: 10.1006/abbi.1994.1024
Taparia, S., Fleet, J. C., Peng, J. B., Xiang, D. W. & Wood, R. J. 1,25-dihydroxyvitamin d and 25-hydroxyvitamin d—mediated regulation of trpv6 (a putative epithelial calcium channel) mrna expression in caco-2 cells. Eur. J. Nutr. 45, 196–204 (2006).
pubmed: 16362534
doi: 10.1007/s00394-005-0586-3
pmcid: 16362534
Wu, W., Zhang, X. & Zanello, L. P. 1α,25-Dihydroxyvitamin D3 antiproliferative actions involve vitamin D receptor-mediated activation of MAPK pathways and AP-1/p21waf1 upregulation in human osteosarcoma. Cancer Lett. 254, 75–86 (2007).
pubmed: 17412493
pmcid: 2760385
doi: 10.1016/j.canlet.2007.02.013
Thompson, L. et al. Effect of 25-hydroxyvitamin D
pubmed: 22042758
doi: 10.1002/jor.21585
pmcid: 22042758
Zayny, A. et al. Effects of glucocorticoids on vitamin D3-metabolizing 24-hydroxylase (CYP24A1) in Saos-2 cells and primary human osteoblasts. Mol. Cell. Endocrinol. 496, 110525 (2019).
pubmed: 31352041
doi: 10.1016/j.mce.2019.110525
pmcid: 31352041
Atkins, G. J. et al. Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine and paracrine activities of 1α,25-dihydroxyvitamin D3. Bone 40, 1517–1528 (2007).
pubmed: 17395559
doi: 10.1016/j.bone.2007.02.024
pmcid: 17395559
Panda, D. K. et al. Inactivation of the 25-hydroxyvitamin d 1α-hydroxylase and vitamin d receptor demonstrates independent and interdependent effects of calcium and vitamin d on skeletal and mineral homeostasis. J. Biol. Chem. 279, 16754–16766 (2004).
pubmed: 14739296
doi: 10.1074/jbc.M310271200
pmcid: 14739296
Jones, G., Prosser, D. E. & Kaufmann, M. 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): Its important role in the degradation of vitamin D. Arch. Biochem. Biophys. 523, 9–18 (2012).
pubmed: 22100522
doi: 10.1016/j.abb.2011.11.003
pmcid: 22100522
Ryhänen, S., Jääskeläinen, T., Saarela, J. T. & Mäenpää, P. H. Inhibition of proliferation and induction of differentiation of osteoblastic cells by a novel 1,25-dihydroxyvitamin d3 analog with an extensively modified side chain (CB1093). J. Cell. Biochem. 70, 414 (1998).
pubmed: 9706878
doi: 10.1002/(SICI)1097-4644(19980901)70:3<414::AID-JCB14>3.0.CO;2-K
pmcid: 9706878
Matsumoto, T. et al. p53-independent induction of WAF1/Cip1 is correlated with osteoblastic differentiation by vitamin D3. Cancer Lett. 129, 61–68 (1998).
pubmed: 9714336
doi: 10.1016/S0304-3835(98)00080-9
pmcid: 9714336
Zenmyo, M. et al. Transcriptional activation of p21 by vitamin D3 or vitamin K2 leads to differentiation of p53-deficient MG-63 osteosarcoma cells. Hum. Pathol. 32, 410–416 (2001).
pubmed: 11331958
doi: 10.1053/hupa.2001.23524
Beresford, J. N., Joyner, C. J., Devlin, C. & Triffitt, J. T. The effects of dexamethasone and 1,25-dihydroxyvitamin D3 on osteogenic differentiation of human marrow stromal cells in vitro. Arch. Oral Biol. 39, 941–947 (1994).
pubmed: 7695507
doi: 10.1016/0003-9969(94)90077-9
pmcid: 7695507
Song, Y. et al. Calcium transporter 1 and epithelial calcium channel messenger ribonucleic acid are differentially regulated by 1,25 dihydroxyvitamin D3 in the intestine and kidney of mice. Endocrinology 144, 3885–3894 (2003).
pubmed: 12933662
doi: 10.1210/en.2003-0314
Lee, G. S., Jung, E. M., Choi, K. C., Oh, G. T. & Jeung, E. B. Compensatory induction of the TRPV6 channel in a calbindin-D9k knockout mouse: Its regulation by 1,25-hydroxyvitamin D3. J. Cell. Biochem. 108, 1175–1183 (2009).
pubmed: 19777446
doi: 10.1002/jcb.22347
pmcid: 19777446
Li, Y. C., Bolt, M. J. G., Cao, L. P. & Sitrin, M. D. Effects of vitamin D receptor inactivation on the expression of calbindins and calcium metabolism. Am. J. Physiol. Endocrinol. Metab. 281, E558 (2001).
pubmed: 11500311
doi: 10.1152/ajpendo.2001.281.3.E558
Balmain, N., Tisserand-Jochem, E., Thomasset, M., Cuisinier-Gleizes, P. & Mathieu, H. Vitamin-D-dependent calcium-binding protein (CaBP-9K) in rat growth cartilage. Histochemistry 84, 161–168 (1986).
pubmed: 3519542
doi: 10.1007/BF00499828
Kim, S., An, B. S., Yang, H. & Jeung, E. B. Effects of octylphenol and bisphenol A on the expression of calcium transport genes in the mouse duodenum and kidney during pregnancy. Toxicology 303, 99–106 (2013).
pubmed: 23142789
doi: 10.1016/j.tox.2012.10.023
pmcid: 23142789
Tocchini-Valentini, G., Rochel, N., Wurtz, J. M., Mitschler, A. & Moras, D. Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands. Proc. Natl. Acad. Sci. USA 98, 5491–5496 (2001).
pubmed: 11344298
doi: 10.1073/pnas.091018698
pmcid: 11344298
Krieger, E. et al. Improving physical realism, stereochemistry, and side-chain accuracy in homology modeling: four approaches that performed well in CASP8. Proteins Struct. Funct. Bioinform. 77, 114–122 (2009).
doi: 10.1002/prot.22570
Trott, O. & Olson, A. J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455–461 (2010).
pubmed: 19499576
pmcid: 3041641
Kurkcuoglu, Z. et al. Performance of HADDOCK and a simple contact-based protein–ligand binding affinity predictor in the D3R Grand Challenge 2. J. Comput. Aided. Mol. Des. 32, 175–185 (2018).
pubmed: 28831657
doi: 10.1007/s10822-017-0049-y
pmcid: 28831657
Kuriata, A. et al. CABS-flex 20: a web server for fast simulations of flexibility of protein structures. Nucl. Acid Res. 46, W338–W343 (2018).
doi: 10.1093/nar/gky356
Jamroz, M., Kolinski, A. & Kmiecik, S. CABS-flex: server for fast simulation of protein structure fluctuations. Nucl. Acids Res. 41, W427–W431 (2013).
pubmed: 23658222
doi: 10.1093/nar/gkt332
pmcid: 23658222
Ferlin, A., Perilli, L., Gianesello, L., Taglialavoro, G. & Foresta, C. Profiling insulin like factor 3 (INSL3) signaling in human osteoblasts. PLoS One 6, e29733 (2011).
pubmed: 22216350
pmcid: 3247287
doi: 10.1371/journal.pone.0029733
Foresta, C. et al. Bone mineral density and testicular failure: evidence for a role of vitamin d 25-hydroxylase in human testis. J. Clin. Endocrinol. Metab. 96, E646–E652 (2011).
pubmed: 21270327
doi: 10.1210/jc.2010-1628