A Species Difference in the Peroxisome Proliferator-Activated Receptor α-Dependent Response to the Developmental Effects of Perfluorooctanoic Acid
Abstract
This study examined the effect of prenatal perfluorooctanoic acid (PFOA) administration on pre- and postnatal development using peroxisome proliferator-activated receptor α (PPARα)-humanized mice to determine if species differences in receptor activity might influence the developmental effects induced by PFOA. Pregnant mice were treated daily with water or PFOA (3mg/kg) by po gavage from gestation day 1 (GD1) until GD17 and then either euthanized on GD18 or allowed to give birth and then euthanized on postnatal day 20 (PND20). No changes in average fetal weight, crown-to-rump length, or placental weight were observed on GD18. Expression of mRNA encoding the PPARα target genes acyl CoA oxidase (Acox1) and cytochrome P450 4a10 (Cyp4a10) in maternal and fetal liver was increased on GD18 in wild-type and PPARα-humanized mice but not in Pparα-null mice. On PND20, relative liver weight was higher in wild-type mice but not in Pparα-null mice or PPARα-humanized mice. Hepatic expression of Acox1 and Cyp4a10 mRNA was higher in wild-type mice but not in Pparα-null mice or PPARα-humanized mice on PND20. The percentage of mice surviving postnatally was lower in wild-type litters but not in litters from Pparα-null mice or PPARα-humanized mice. No changes in pup weight gain, onset of eye opening, or mammary gland development were found in any genotype. Results from these studies demonstrate that the developmental/postnatal effects resulting from prenatal PFOA exposure in mice are differentially mediated by mouse and human PPARα.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Prenatal PFOA effects on development depend on mouse and human PPARα differences.
“These findings suggest that prenatal PFOA effects on development depends on mouse and human PPARα differences [36].”
From The EU’s Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science (2023) · cites this paper as [36]
Cites
Sources, fate and transport of perfluorocarboxylates
Prevedouros, K., Cousins, I. T., Buck, R. C., & Korzeniowski, S. H. (2006) · Environmental Science & Technology · doi:10.1021/es0512475 · Cited by 2,594 · see citing works
Lee, S. S. T., Pineau, T., Drago, J., Lee, E. J., Owens, J. W., Kroetz, D. L., Fernández‐Salguero, P. M., Westphal, H., & Gonzalez, F. J. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.6.3012 · Cited by 1,655 · see citing works
Self-citationThe toxicology of perfluorooctanoate
Kennedy, G. L., Butenhoff, J. L., Olsen, G. W., O'Connor, J. C., Seacat, A. M., Perkins, R. G., Biegel, L. B., Murphy, S. R., & Farrar, D. G. (2004) · Critical Reviews in Toxicology · doi:10.1080/10408440490464705 · Cited by 742 · see citing works
Self-citationEpidemiologic Evidence on the Health Effects of Perfluorooctanoic Acid (PFOA)
Steenland, K., Fletcher, T., & Savitz, D. A. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.0901827 · Cited by 660 · see citing works
PPARα Agonist-Induced Rodent Tumors: Modes of Action and Human Relevance
Klaunig, J. E., Babich, M. A., Baetcke, K. P., Cook, J. C., Corton, J. C., David, R. M., DeLuca, J. G., Lai, D. Y., McKee, R. H., Peters, J. M., et al. (2003) · Critical Reviews in Toxicology · doi:10.1080/713608372 · Cited by 611 · see citing works
Self-citationEffects of perfluorooctanoic acid exposure during pregnancy in the mouse.
Lau, C., Thibodeaux, J. R., Hanson, R., Narotsky, M., Rogers, J. M., Lindstrom, A., & Strynar, M. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfj105 · Cited by 547 · see citing works
The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention
Peters, J. M., Shah, Y. M., & Gonzalez, F. J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3214 · Cited by 494 · see citing works
Self-citationPeters, J. (1997) · Carcinogenesis · doi:10.1093/carcin/18.11.2029 · Cited by 484 · see citing works
Self-citationHeuvel, J. P. V., Thompson, J. T., Frame, S. R., & Gillies, P. J. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfl014 · Cited by 479 · see citing works
Self-citationtrans-Activation of PPARα and PPARγ by Structurally Diverse Environmental Chemicals
Maloney, E. K., & Waxman, D. J. (1999) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1999.8809 · Cited by 375 · see citing works
Abbott, B. D., Wolf, C. J., Schmid, J., Das, K. P., ZEHR, R. D. J., Helfant, L., Nakayama, S. F., Lindstrom, A. B., Strynar, M. J., & Lau, C. S. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm110 · Cited by 262 · see citing works
Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes
Bjork, J. A., Butenhoff, J. L., & Wallace, K. B. (2011) · Toxicology · doi:10.1016/j.tox.2011.06.012 · Cited by 260 · see citing works
Self-citationShah, Y. M., Morimura, K., Yang, Q., Tanabe, T., Takagi, M., & Gonzalez, F. J. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00317-07 · Cited by 255 · see citing works
Self-citationPeroxisome proliferator-activated receptor-α and liver cancer: where do we stand?
Peters, J. M., Cheung, C., & Gonzalez, F. J. (2005) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0678-9 · Cited by 248 · see citing works
Self-citationD’eon, J. C., & Mabury, S. A. (2011) · Environmental Science & Technology · doi:10.1021/es200171y · Cited by 238 · see citing works
Bility, M. T. (2004) · Toxicological Sciences · doi:10.1093/toxsci/kfh253 · Cited by 231 · see citing works
White, S., Calafat, A., Kuklenyik, Z., Villanueva, L. R., Zehr, R. D., Helfant, L., Strynar, M., Lindstrom, A., Thibodeaux, J. R., Wood, C., et al. (2006) · Toxicological Sciences · doi:10.1093/toxsci/kfl177 · Cited by 229 · see citing works
Cheung, C., Akiyama, T., Ward, J., Nicol, C., Feigenbaum, L., Vinson, C., & Gonzalez, F. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0322 · Cited by 224 · see citing works
Self-citationRosen, M. B., Lee, J. S., Ren, H., Vallanat, B., Liu, J., Waalkes, M. P., Abbott, B. D., Lau, C. S., & Corton, J. C. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn025 · Cited by 200 · see citing works
Yang, Q., Nagano, T., Shah, Y. M., Cheung, C., Ito, S., & Gonzalez, F. J. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm206 · Cited by 180 · see citing works
Self-citationMorimura, K., Cheung, C., Ward, J. M., Reddy, J. K., & Gonzalez, F. J. (2005) · Carcinogenesis · doi:10.1093/carcin/bgi329 · Cited by 168 · see citing works
Self-citationPeters, J. M. (1998) · Carcinogenesis · doi:10.1093/carcin/19.11.1989 · Cited by 161 · see citing works
Self-citationWolf, C. J., Schmid, J. E., Lau, C. S., & Abbott, B. D. (2011) · Reproductive Toxicology · doi:10.1016/j.reprotox.2011.09.009 · Cited by 160 · see citing works
Hays, T. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh285 · Cited by 130 · see citing works
Akiyama, T. E., Nicol, C. J. B., Fiévet, C., Staels, B., Ward, J. M., Auwerx, J. H., Lee, S. S. T., Gonzalez, F. J., & Peters, J. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m107073200 · Cited by 121 · see citing works
Self-citationZhao, Y. M., Tan, Y., Haslam, S. Z., & Yang, C. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq030 · Cited by 105 · see citing works
Cheng, X., & Klaassen, C. D. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn147 · Cited by 102 · see citing works
Ren, H., Vallanat, B., Nelson, D. M., Yeung, L. W. Y., Guruge, K. S., Lam, P. K. S., Lehman‐McKeeman, L. D., & Corton, J. C. (2009) · Reproductive Toxicology · doi:10.1016/j.reprotox.2008.12.011 · Cited by 97 · see citing works
Elcombe, C. R., Elcombe, B. M., Foster, J. R., Farrar, D. G., Jung, R., Chang, S.-C., Kennedy, G. L., & Butenhoff, J. L. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0572-2 · Cited by 96 · see citing works
Self-citationYang, C., Tan, Y., Harkema, J. R., & Haslam, S. Z. (2008) · Reproductive Toxicology · doi:10.1016/j.reprotox.2008.10.003 · Cited by 87 · see citing works
Butenhoff, J. L., Bjork, J. A., Chang, S.-C., Ehresman, D. J., Parker, G. A., Das, K., Lau, C., Lieder, P. H., van Otterdijk, F. M., & Wallace, K. B. (2012) · Reproductive Toxicology · doi:10.1016/j.reprotox.2011.08.004 · Cited by 75 · see citing works
Self-citationNakamura, T., Ito, Y., Yanagiba, Y., Ramdhan, D. H., Kono, Y., Naito, H., Hayashi, Y., Li, Y., Aoyama, T., Gonzalez, F. J., et al. (2009) · Toxicology · doi:10.1016/j.tox.2009.09.004 · Cited by 57 · see citing works
Self-citationHovey, R. C., Coder, P. S., Wolf, J. C., Sielken, R. L., Tisdel, M. O., & Breckenridge, C. B. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq337 · Cited by 38 · see citing works
Palkar, P. S., Anderson, C. R., Ferry, C. H., Gonzalez, F. J., & Peters, J. M. (2010) · Toxicology · doi:10.1016/j.tox.2010.07.008 · Cited by 15 · see citing works
Self-citationEffects of Postnatal Litter Size on Reproduction of Female Mice
Nelson, R. E., & Robison, O. W. (1976) · Journal of Animal Science · doi:10.2527/jas1976.424824x · Cited by 14 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals
Gore, A. C., Chappell, V. A., Fenton, S. E., Flaws, J. A., Nadal, A., Prins, G. S., Toppari, J., & Zoeller, R. T. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1010 · Cited by 2,407 · see citing works
Risk to human health related to the presence of perfluoroalkyl substances in food
Panel), E. P. O. C. I. T. F. C. (. C., Schrenk, D., Bignami, M., Bodin, L., Chipman, J. K., del Mazo, J., Grasl‐Kraupp, B., Hogstrand, C., Hoogenboom, L. (., Leblanc, J., et al. (2020) · EFSA Journal · doi:10.2903/j.efsa.2020.6223 · Cited by 989 · see citing works
Borg, D., Lund, B.-O., Lindquist, N.-G., & Håkansson, H. (2013) · Environment International · doi:10.1016/j.envint.2013.05.009 · Cited by 155 · see citing works
The EU’s Per- and Polyfluoroalkyl Substances (PFAS) Ban: A Case of Policy over Science
Spyrakis, F., & Dragani, T. A. (2023) · Toxics · doi:10.3390/toxics11090721 · Cited by 78 · see citing works
- Authors
- Albrecht, P. P., Torsell, N. E., Krishnan, P., Ehresman, D. J., Frame, S. R., Chang, S.-C., Butenhoff, J. L., Kennedy, G. L., Gonzalez, F. J., & Peters, J. M.
- Affiliations
- Pennsylvania State University (US)
- 3M (United States) (US)
- DuPont (United States) (US)
- National Institutes of Health (US)
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-11-09
- Volume
- 131
- Issue
- 2
- Pages
- 568-582
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- OpenAlex
- W2170150815
- Cited by
- 44
- References
- 35
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 7 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 7 · 2013: 4
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicological Sciences (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- perfluorooctanoic acid, PPARα, species differences, prenatal exposure, developmental toxicity, PPARalpha-null mice, ACOX1, Cyp4a10, hepatic gene expression, fetal liver, postnatal survival, perfluorinated compounds
- MeSH terms
- Animals, Caprylates, Female, Fluorocarbons, Humans, Pregnancy, Species Specificity, Mice, Knockout, PPAR alpha, Mice, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
