Effects of In Utero and Lactational TCDD Exposure on Bone Development in Differentially Sensitive Rat Lines

Miettinen, Hanna; Pulkkinen, Pasi; Jämsä, Timo; Koistinen, Jaana; Simanainen, Ulla; Tuomisto, Jouko; Tuukkanen, Juha; Viluksela, Matti

doi:10.1093/toxsci/kfi136

Cited by 85 publications

(69 citation statements)

References 39 publications

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“…In contrast, the female offspring (ewes) exhibited no changes in pQCT variables but the three-point bending test, however, showed that the exposed ewes in the present study had more fragile bone (lower load at failure and reduced stiffness) than the C ewes. Similar reductions in bone strength have been reported previously in studies of rats exposed to dioxin and dioxin like PCBs (Jamsa et al, 2001;Lind et al, 2000b;Miettinen et al, 2005) and a PCB mixture (Andrews, 1989).…”

Section: Discussionsupporting

confidence: 86%

“…Since many EDCs have oestrogenic effects, the potential significance of increasing exposure to environmental oestrogens with respect to bone density is of public health interest. Evidence of effects on bone structure of exposure to a range of pollutant classes has been derived, in part, from empirical studies designed to investigate effects of exposure and mechanisms of action using laboratory animals Hermsen et al, 2008;Jamsa et al, 2001;Lind et al, 1999;Lind et al, 2000b;Miettinen et al, 2005;Yilmaz et al, 2006) and domestic animals (Lundberg et al, 2006). Most of these studies concern exposure to abnormally high concentrations of the chemicals concerned.…”

Section: Introductionmentioning

confidence: 99%

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Exposure to pastures fertilised with sewage sludge disrupts bone tissue homeostasis in sheep

Lind¹,

Gustafsson²,

Hermsen³

et al. 2009

Science of The Total Environment

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The femurs of male and female sheep (Ovis aries), aged 18 months, bred on pastures fertilized twice annually with sewage sludge (2.25 tonnes dry matter/ha; Treated; T)) or on pastures treated with inorganic fertilizer (Control; C) were studied, using peripheral Quantitative Computed Tomography (pQCT) and the three-point bending test. Males were maintained on the respective treatments from conception to weaning and then maintained on control pastures while the females were maintained on the respective treatments until slaughter.T rams exhibited increased total bone mineral density (BMD) at the metaphyseal part of femur (+ 10.5%, p b 0.01) compared with C rams but had a reduced total cross sectional area IntroductionThe application of sewage sludge to land is likely to increase in both Europe and the United States as a dumping at sea is banned and land-fill sites become less available (Rhind et al., 2005b;Swanson et al., 2004). However, sludge contains high concentrations of many environmental pollutants including endocrine disrupting compounds (EDCs) such as alkyl phenols, phthalates, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDE), polycyclic aromatic hydrocarbons (PAH), dioxins, pesticides and toxic metals (Brunner et al., 1988;Ghanem et al., 2007;Giger et al., 1984;Stevens et al., 2003). Since these are known to exert adverse effects on animal and human physiology and health (IEH, 1999;Toppari et al., 1996), potential effects on wildlife, domestic animals and humans are of concern. Theoretical and empirical studies, designed to investigate the issue of accumulation of pollutants in domestic animal

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Exposure to pastures fertilised with sewage sludge disrupts bone tissue homeostasis in sheep

Lind¹,

Gustafsson²,

Hermsen³

et al. 2009

Science of The Total Environment

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“…Developmental exposure to TCDD in rats adversely affects the structural and mechanical properties of bone (Miettinen et al, 2005), and numerous in vitro studies have confirmed TCDD-mediated inhibition of osteoblast differentiation in murine cell models (Gierthy et al, 1994;Korkalainen et al, 2009;Ryan et al, 2007;Singh et al, 2000;Yu et al, 2014). In humans, elevated exposure to polychlorinated dibenzo-p-dioxins and furans during breastfeeding has been strongly associated with hypomineralization of teeth (Alaluusua et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

From the Cover: Embryonic Exposure to TCDD Impacts Osteogenesis of the Axial Skeleton in Japanese medaka,Oryzias latipes

Watson¹,

Planchart

Mattingly

et al. 2016

Toxicol. Sci.

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Recent studies from mammalian, fish, and in vitro models have identified bone and cartilage development as sensitive targets for dioxins and other aryl hydrocarbon receptor ligands. In this study, we assess how embryonic 2,3,7,8-tetrachlorochlorodibenzo-p-dioxin (TCDD) exposure impacts axial osteogenesis in Japanese medaka (Oryzias latipes), a vertebrate model of human bone development. Embryos from inbred wild-type Orange-red Hd-dR and 3 transgenic medaka lines (twist:EGFP, osx/sp7:mCherry, col10a1:nlGFP) were exposed to 0.15 nM and 0.3 nM TCDD and reared until 20 dpf. Individuals were stained for mineralized bone and imaged using confocal microscopy to assess skeletal alterations in medial vertebrae in combination with a qualitative spatial analysis of osteoblast and osteoblast progenitor cell populations. Exposure to TCDD resulted in an overall attenuation of vertebral ossification characterized by truncated centra, and reduced neural and hemal arch lengths. Effects on mineralization were consistent with modifications in cell number and cell localization of transgene-labeled osteoblast and osteoblast progenitor cells. Endogenous expression of osteogenic regulators runt-related transcription factor 2 (runx2) and osterix (osx/sp7), and extracellular matrix genes osteopontin (spp1), collagen type I alpha I (col1), collagen type X alpha I (col10a1), and osteocalcin (bglap/osc) was significantly diminished at 20 dpf following TCDD exposure as compared with controls. Through global transcriptomic analysis more than 590 differentially expressed genes were identified and mapped to select pathological states including inflammatory disease, connective tissue disorders, and skeletal and muscular disorders. Taken together, results from this study suggest that TCDD exposure inhibits axial bone formation through dysregulation of osteoblast differentiation. This approach highlights the advantages and sensitivity of using small fish models to investigate how xenobiotic exposure may impact skeletal development.

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“…Effects of PCB (Andrews, 1989;Hoffman et al, 1996;Lind et al, 1999Lind et al, , 2000Lundberg et al, 2006) and PCDD (Jämsä et al, 2001;Miettinen et al, 2005) on bone tissue include decreased length and cross-sectional area, alterations in mineral density, and decreased strength following controlled exposure. The mineral density of skull bones of East Greenland polar bears was negatively related to PCBs, polybrominated diphenyl ethers (PBDEs), and other organohalogen pollutants (Sonne et al, 2004).…”

Section: Locationmentioning

confidence: 99%

“…The metals cadmium (Bhattacharyya et al, 1988), aluminum (Hahn, 1989;Firling et al, 1999), and lead (Potula et al, 2006) are known to induce harmful effects on bone tissue. Experimental studies suggest that bone tissue could be an important target for a number of endocrine-disrupting persistent organohalogen pollutants, including hexachlorobenzene (Andrews et al, 1988), polychlorinated biphenyls (PCBs) (Andrews, 1989;Hoffman et al, 1996;Lind et al, 1999Lind et al, , 2000Lundberg et al, 2006), and polychlorinated dibenzo-p-dioxins (PCDD) (Jämsä et al, 2001;Miettinen et al, 2005).…”

mentioning

confidence: 99%

Health of Herring Gulls (Larus argentatus) in Relation to Breeding Location in the Early 1990s. III. Effects on the Bone Tissue

Fox¹,

Lundberg²,

Wejheden³

et al. 2008

Journal of Toxicology and Environmental Health, Part A

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Health effects associated with the Great Lakes environment were assessed in adult herring gulls (Larus argentatus) in the early 1990s, including the size and quality of their bones. Femurs were excised from 140 individuals from 10 colonies distributed throughout the Great Lakes and 2 reference colonies in Lake Winnipeg (freshwater) and the Bay of Fundy (marine). Femurs of gulls from the Great Lakes differed from the freshwater or marine reference for 9 of 12 variables of size, composition, and strength assessed using peripheral quantitative computed tomography (pQCT) and biomechanical testing. Femurs of Great Lakes gulls were significantly smaller in length (−2.9%), periosteal circumference (−2.4%), and crosssectional area (−5.4%) than freshwater reference birds. Femurs of the Great Lakes gulls had a lower significant cortical bone mineral content (−8.1%) and density (−2%) than the marine reference. A significant increase in the amount the bone could bend before it broke (+34%) and the energy required to break it (+44%) and a significant decrease (−16.3%) in stiffness during three-point biomechanical bending test were also detected in Great Lakes versus the freshwater gulls. These differences are indicative of impaired mineralization. When divided into high and low 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TCDD-TEQ) colonies, the amount the bone could bend before it broke and the energy required to break it were significantly higher in the high TEQ colonies, but not high polychlorinated biphenyl (PCB) colonies. Breeding location and dietary choices of Great Lakes herring gulls in the early 1990s resulted in modulations of physiological processes that affected the size, mineralization, and biomechanical properties of bone.

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Effects of In Utero and Lactational TCDD Exposure on Bone Development in Differentially Sensitive Rat Lines

Cited by 85 publications

References 39 publications

Exposure to pastures fertilised with sewage sludge disrupts bone tissue homeostasis in sheep

Exposure to pastures fertilised with sewage sludge disrupts bone tissue homeostasis in sheep

From the Cover: Embryonic Exposure to TCDD Impacts Osteogenesis of the Axial Skeleton in Japanese medaka,Oryzias latipes

Health of Herring Gulls (Larus argentatus) in Relation to Breeding Location in the Early 1990s. III. Effects on the Bone Tissue

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