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Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats
BACKGROUND: Hexafluoropropylene oxide dimer acid [(HFPO-DA), GenX] is a member of the per- and polyfluoroalkyl substances (PFAS) chemical class, and elevated levels of HFPO-DA have been detected in surface water, air, and treated drinking water in the United States and Europe. OBJECTIVES: We aimed t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Environmental Health Perspectives
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768323/ https://www.ncbi.nlm.nih.gov/pubmed/30920876 http://dx.doi.org/10.1289/EHP4372 |
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author | Conley, Justin M. Lambright, Christy S. Evans, Nicola Strynar, Mark J. McCord, James McIntyre, Barry S. Travlos, Gregory S. Cardon, Mary C. Medlock-Kakaley, Elizabeth Hartig, Phillip C. Wilson, Vickie S. Gray, L. Earl |
author_facet | Conley, Justin M. Lambright, Christy S. Evans, Nicola Strynar, Mark J. McCord, James McIntyre, Barry S. Travlos, Gregory S. Cardon, Mary C. Medlock-Kakaley, Elizabeth Hartig, Phillip C. Wilson, Vickie S. Gray, L. Earl |
author_sort | Conley, Justin M. |
collection | PubMed |
description | BACKGROUND: Hexafluoropropylene oxide dimer acid [(HFPO-DA), GenX] is a member of the per- and polyfluoroalkyl substances (PFAS) chemical class, and elevated levels of HFPO-DA have been detected in surface water, air, and treated drinking water in the United States and Europe. OBJECTIVES: We aimed to characterize the potential maternal and postnatal toxicities of oral HFPO-DA in rats during sexual differentiation. Given that some PFAS activate peroxisome proliferator-activated receptors (PPARs), we sought to assess whether HFPO-DA affects androgen-dependent development or interferes with estrogen, androgen, or glucocorticoid receptor activity. METHODS: Steroid receptor activity was assessed with a suite of in vitro transactivation assays, and Sprague-Dawley rats were used to assess maternal, fetal, and postnatal effects of HFPO-DA exposure. Dams were dosed daily via oral gavage during male reproductive development (gestation days 14–18). We evaluated fetal testes, maternal and fetal livers, maternal serum clinical chemistry, and reproductive development of F1 animals. RESULTS: HFPO-DA exposure resulted in negligible in vitro receptor activity and did not impact testosterone production or expression of genes key to male reproductive development in the fetal testis; however, in vivo exposure during gestation resulted in higher maternal liver weights ([Formula: see text]), lower maternal serum thyroid hormone and lipid profiles ([Formula: see text]), and up-regulated gene expression related to PPAR signaling pathways in maternal and fetal livers ([Formula: see text]). Further, the pilot postnatal study indicated lower female body weight and lower weights of male reproductive tissues in F1 animals. CONCLUSIONS: HFPO-DA exposure produced multiple effects that were similar to prior toxicity evaluations on PFAS, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), but seen as the result of higher oral doses. The mean dam serum concentration from the lowest dose group was 4-fold greater than the maximum serum concentration detected in a worker in an HFPO-DA manufacturing facility. Research is needed to examine the mechanisms and downstream events linked to the adverse effects of PFAS as are mixture-based studies evaluating multiple PFAS. https://doi.org/10.1289/EHP4372 |
format | Online Article Text |
id | pubmed-6768323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Environmental Health Perspectives |
record_format | MEDLINE/PubMed |
spelling | pubmed-67683232019-10-02 Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats Conley, Justin M. Lambright, Christy S. Evans, Nicola Strynar, Mark J. McCord, James McIntyre, Barry S. Travlos, Gregory S. Cardon, Mary C. Medlock-Kakaley, Elizabeth Hartig, Phillip C. Wilson, Vickie S. Gray, L. Earl Environ Health Perspect Research BACKGROUND: Hexafluoropropylene oxide dimer acid [(HFPO-DA), GenX] is a member of the per- and polyfluoroalkyl substances (PFAS) chemical class, and elevated levels of HFPO-DA have been detected in surface water, air, and treated drinking water in the United States and Europe. OBJECTIVES: We aimed to characterize the potential maternal and postnatal toxicities of oral HFPO-DA in rats during sexual differentiation. Given that some PFAS activate peroxisome proliferator-activated receptors (PPARs), we sought to assess whether HFPO-DA affects androgen-dependent development or interferes with estrogen, androgen, or glucocorticoid receptor activity. METHODS: Steroid receptor activity was assessed with a suite of in vitro transactivation assays, and Sprague-Dawley rats were used to assess maternal, fetal, and postnatal effects of HFPO-DA exposure. Dams were dosed daily via oral gavage during male reproductive development (gestation days 14–18). We evaluated fetal testes, maternal and fetal livers, maternal serum clinical chemistry, and reproductive development of F1 animals. RESULTS: HFPO-DA exposure resulted in negligible in vitro receptor activity and did not impact testosterone production or expression of genes key to male reproductive development in the fetal testis; however, in vivo exposure during gestation resulted in higher maternal liver weights ([Formula: see text]), lower maternal serum thyroid hormone and lipid profiles ([Formula: see text]), and up-regulated gene expression related to PPAR signaling pathways in maternal and fetal livers ([Formula: see text]). Further, the pilot postnatal study indicated lower female body weight and lower weights of male reproductive tissues in F1 animals. CONCLUSIONS: HFPO-DA exposure produced multiple effects that were similar to prior toxicity evaluations on PFAS, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), but seen as the result of higher oral doses. The mean dam serum concentration from the lowest dose group was 4-fold greater than the maximum serum concentration detected in a worker in an HFPO-DA manufacturing facility. Research is needed to examine the mechanisms and downstream events linked to the adverse effects of PFAS as are mixture-based studies evaluating multiple PFAS. https://doi.org/10.1289/EHP4372 Environmental Health Perspectives 2019-03-28 /pmc/articles/PMC6768323/ /pubmed/30920876 http://dx.doi.org/10.1289/EHP4372 Text en EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. |
spellingShingle | Research Conley, Justin M. Lambright, Christy S. Evans, Nicola Strynar, Mark J. McCord, James McIntyre, Barry S. Travlos, Gregory S. Cardon, Mary C. Medlock-Kakaley, Elizabeth Hartig, Phillip C. Wilson, Vickie S. Gray, L. Earl Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats |
title | Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats |
title_full | Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats |
title_fullStr | Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats |
title_full_unstemmed | Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats |
title_short | Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats |
title_sort | adverse maternal, fetal, and postnatal effects of hexafluoropropylene oxide dimer acid (genx) from oral gestational exposure in sprague-dawley rats |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768323/ https://www.ncbi.nlm.nih.gov/pubmed/30920876 http://dx.doi.org/10.1289/EHP4372 |
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