Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation

Koskela, Antti; Finnilä, Mikko A. J.; Korkalainen, Merja; Spulber, Ştefan; Koponen, Jani; Håkansson, Helen; Tuukkanen, Juha; Viluksela, Matti

doi:10.1016/j.taap.2016.04.002

Cited by 60 publications

(54 citation statements)

References 41 publications

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“…In vitro studies showed similar effects of PFOA on differentiation of human osteoclasts as in our previous study in mouse osteoclasts 15 . The studied concentrations include the range of levels analyzed in Spanish bone samples 12 , and are therefore environmentally relevant.…”

Section: Discussionsupporting

confidence: 85%

“…In the adult US population, a negative association between serum PFOS and PFOA concentration and bone mineral density has been reported in cross-sectional studies 13, 14 . In our recent study, in utero and lactational exposure to PFOA in mice led to significantly higher PFOA levels in long bones even at the age of 17 months, and we showed dose-dependent effects on mouse osteoclasts and osteoblasts in vitro 15 .…”

Section: Introductionsupporting

confidence: 61%

“…In BMD calculations, the EC50-concentration for human osteoclast resorption activity was 0.49 µM, whereas the EC50 in mouse osteoclast resorption activity calculated from our previous study 15 , was 0.27 µM. Due to biological variation, no BMD could be reliably modeled from the number of osteoclasts in human, but in mice, the response was clearly more sensitive as the EC50 was 0.001 µM.…”

Section: Resultsmentioning

confidence: 80%

“…PFOA concentrations of human bones and mouse bones from our earlier study 15 are summarized and compared to the lowest observed adverse effect levels (LOAEL) and no-observed adverse effect levels (NOAEL) from in vivo and in vitro studies in Table 2. For comparison, serum PFOA concentrations of general population and firefighters with potential occupational exposure are also shown.…”

Section: Resultsmentioning

confidence: 99%

“…All the samples of femoral head and cadaver tissue were pretreated for chemical analyses as described previously 15 . The concentration of 11 PFAS (PFOA, PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), perfluorododecanoic acid (PFDoA), perfluorotridecanoic acid (PFTrA), perfluorotetradecanoic acid (PFTeA), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), and PFDS (perfluorodecane sulfonate) were analyzed with liquid chromatography negative ion electrospray tandem mass-spectrometry (LC-ESI-MS/MS) as described previously 38 .…”

Section: Methodsmentioning

confidence: 99%

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Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation

Koskela

Koponen

Lehenkari

et al. 2017

Sci Rep

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Perfluoroalkyl substances (PFAS), including two most commonly studied compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are widely distributed environmental pollutants, used extensively earlier. Due to their toxicological effects the use of PFAS is now regulated. Based on earlier studies on PFOA’s distribution in bone and bone marrow in mice, we investigated PFAS levels and their possible link to bone microarchitecture of human femoral bone samples (n = 18). Soft tissue and bone biopsies were also taken from a 49-year old female cadaver for PFAS analyses. We also studied how PFOA exposure affects differentiation of human osteoblasts and osteoclasts. PFAS were detectable from all dry bone and bone marrow samples, PFOS and PFOA being the most prominent. In cadaver biopsies, lungs and liver contained the highest concentrations of PFAS, whereas PFAS were absent in bone marrow. Perfluorononanoic acid (PFNA) was present in the bones, PFOA and PFOS were absent. In vitro results showed no disturbance in osteogenic differentiation after PFOA exposure, but in osteoclasts, lower concentrations led to increased resorption, which eventually dropped to zero after increase in PFOA concentration. In conclusion, PFAS are present in bone and have the potential to affect human bone cells partly at environmentally relevant concentrations.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionsupporting

confidence: 61%

Section: Resultsmentioning

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation

Koskela

Koponen

Lehenkari

et al. 2017

Sci Rep

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Perfluorooctanoic acid inhibits the maturation rate of mouse oocytes cultured in vitro by triggering mitochondrial and DNA damage

Guo

Zhao

et al. 2021

Birth Defects Research

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Background Perfluorooctanoic acid (PFOA) is widely used in the manufacture of household and industrial products. It has certain toxicity and leaves many residues in the environment. Numerous studies have shown that PFOA exhibits endocrine disrupting properties and immunotoxicity and induces developmental defects. However, there is very little information regarding its toxicity on oocytes. Methods We cultured denuded oocytes in maturation medium supplemented with 0, 300, or 500 PFOA during IVM and evaluated the maturation of oocytes from the aspects of ROS(DCFH‐DA), mitochondria(MitoOrange and JC‐1), DNA damage(P‐H2AX), and cytoskeleton(β‐tubulin). Results Compared with the control group, the PFOA treatment group exhibited significantly reduced proportion of oocytes matutation. Furthermore, the DCFH‐DA test showed that PFOA significantly increased reactive oxygen species (ROS) levels. PFOA disrupted mitochondrial distribution and decreased mitochondrial function as assessed using MitoOrange and JC‐1. In addition, PFOA‐treated oocytes exhibited a significantly higher percentage of P‐H2AX, defective β‐tubulin, abnormal chromosome alignment, lower expression of the anti‐apoptotic gene Bcl‐2, and higher expression of the apoptotic genes caspase3 and Bax. Conclusion In summary, PFOA could negatively and directly affect oocyte maturation in vitro and cause oxidative stress, mitochondrial function disruption, DNA damage, cytoskeleton damage, and apoptosis.

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Recent US State and Federal Drinking Water Guidelines for Per‐ and Polyfluoroalkyl Substances

Post

2020

Enviro Toxic and Chemistry

112

100

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Per-and polyfluoroalkyl substances (PFAS), a class of synthetic chemicals produced for over 70 years, are of increasing concern because of their widespread environmental presence, extreme persistence, bioaccumulative nature, and evidence for health effects from environmentally relevant exposures. In 2016, the United States Environmental Protection Agency (USEPA) established nonregulatory drinking water Health Advisories of 70 ng/L for individual and total concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the 8-carbon perfluoroalkyl acids (PFAAs) that are the most thoroughly studied PFAS. As of May 2020, 9 US states had concluded that the USEPA Health Advisories are insufficiently protective and developed more stringent PFOA and PFOS guidelines. In addition, 10 states had developed guidelines for other PFAS, primarily PFAAs. This Critical Review discusses the scientific basis for state and USEPA drinking water guidelines for PFOA and PFOS; the same principles apply to guidelines for other PFAS. Similarities and differences among guidelines arise from both toxicity and exposure considerations. The approximately 4-fold range among state guidelines (8-35 ng/L for PFOA, 10-40 ng/L for PFOS) is not large or unexpected for guidelines developed by different scientists at different time points, especially when compared with older USEPA and state guidelines that were generally several orders of magnitude higher. Additional state guidelines for PFOA, PFOS, and other PFAS are expected to become available.

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Effects of developmental exposure to perfluorooctanoic acid (PFOA) on long bone morphology and bone cell differentiation

Cited by 60 publications

References 41 publications

Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation

Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation

Perfluorooctanoic acid inhibits the maturation rate of mouse oocytes cultured in vitro by triggering mitochondrial and DNA damage

Recent US State and Federal Drinking Water Guidelines for Per‐ and Polyfluoroalkyl Substances

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