To Tributyltin Research Articles

Molecular and biochemical responses to tributyltin (TBT) exposure in the American oyster: Triggers of stress-induced oxidative DNA damage and prooxidant-antioxidant imbalance in tissues by TBT

Environmental pollution increases due to anthropogenic activities. Toxic chemicals in the environment affect the health of aquatic organisms. Tributyltin (TBT) is a toxic chemical widely used as an antifouling paint on boats, hulls, and ships. The toxic effect of TBT is well documented in aquatic organisms; however, little is known about the effects of TBT on DNA lesions in shellfish. The American oyster (Crassostrea virginica, an edible and commercially important species) is an ideal marine mollusk to examine the effects of TBT exposure on DNA lesions and oxidative/nitrative stress. In this study, we investigated the effects of TBT on 8′-hydroxy-2′-deoxyguanosine (8-OHdG, a biomarker of pro-mutagenic DNA lesion), double-stranded DNA (dsDNA), dinitrophenyl protein (DNP, a biomarker on reactive oxygen species, ROS), 3-nitrotyrosine protein (NTP, a biomarker of reactive nitrogen species, RNS), catalase (CAT, an antioxidant), and acetylcholinesterase (AChE, a cholinergic enzyme) expressions in the gills and digestive glands of oysters. We also analyzed extrapallial (EF) fluid conditions. Immunohistochemical and qRT-PCR results showed that TBT exposure significantly increased 8-OHdG, dsDNA, DNP, NTP, and CAT mRNA and/or protein expressions in the gills and digestive glands. However, AChE mRNA and protein expressions, and EP fluid pH and protein concentrations were decreased in TBT-exposed oysters. Taken together, these results suggest that antifouling biocide-induced production of ROS/RNS results in DNA damage, which may lead to decreased cellular functions in oysters. To the best of our knowledge, the present study provides the first molecular/biochemical evidence that TBT exposure results in oxidative/nitrative stress and DNA lesions in oysters.

Transient developmental exposure to tributyltin reduces optomotor responses in larval zebrafish (Danio rerio)

This study determined the effects of transient developmental exposure to tributyltin (TBT), a well-known anti-estrogenic environmental endocrine disrupting compound, on visual system development of larval zebrafish (Danio rerio). Zebrafish were exposed to either 0.2 μg/L or 20 μg/L TBT for 24 h when they were aged 24 h postfertilization (hpf), 72 hpf, or 7 days (d)pf. Immediately after exposure, larvae were transferred to system water for seven days of recovery followed by behavioral testing (startle and optomotor responses) and morphological assessment. TBT-treated larvae displayed age-dependent changes in morphology characterized by delayed/reduced growth and susceptibility to exposure. TBT exposure reduced the number of larvae displaying optomotor responses regardless of age of exposure; eye diameter was also decreased when exposure occurred at 24 hpf or 7 dpf. Startle responses were reduced only in TBT-treated larvae exposed when they were 24 hpf, suggesting transient TBT exposure during the early larval period may cause vision-specific effects.

Comparison of biomarker responses after acute and chronic bioassays in Lumbriculus variegatus

Differential biomarker responses may occur after acute or chronic bioassays when animals are unfed. In many aquatic species, food deprivation may lead to a pro-oxidant condition. However, information about its effects on the oligochaete Lumbriculus variegatus, a bioindicator organism for water and sediment toxicity tests, is almost completely lacking. Acute (48 h) and chronic (21 days) bioassays were performed using unfed L. variegatus to assess the impact of food deprivation on several biomarkers related to the redox cellular status. Results showed that food deprivation inhibited the antioxidant enzymes superoxide dismutase and catalase, whilst levels of total glutathione (t-GSH) and lipid peroxidation processes increased with respect to controls. The same biomarkers were evaluated in unfed organisms exposed to tributyltin (TBT), nano-goethite or a binary mixture of both, for 48 h and 21 days. After 48 h, the organisms were able to cope with chemical stressors by enhancing antioxidant defences and lipid peroxidation processes were not observed. After 21 days, both TBT and the binary mixture induced the most noxious effects. At this time, the antioxidant enzymatic defences were still higher than controls, but levels of t-GSH were significantly decreased and lipid peroxidation was found. Therefore, differential biomarker responses were observed between starved organisms for 21 days and those simultaneously exposed to other chemical stressors. The activity of the enzyme acetylcholinesterase was also determined, but it remained unchanged in all cases.

Transgenerational Self-Reconstruction of Disrupted Chromatin Organization After Exposure To An Environmental Stressor in Mice

Exposure to environmental stressors is known to increase disease susceptibility in unexposed descendants in the absence of detectable genetic mutations. The mechanisms mediating environmentally-induced transgenerational disease susceptibility are poorly understood. We showed that great-great-grandsons of female mice exposed to tributyltin (TBT) throughout pregnancy and lactation were predisposed to obesity due to altered chromatin organization that subsequently biased DNA methylation and gene expression. Here we analyzed DNA methylomes and transcriptomes from tissues of animals ancestrally exposed to TBT spanning generations, sexes, ontogeny, and cell differentiation state. We found that TBT elicited concerted alterations in the expression of “chromatin organization” genes and inferred that TBT-disrupted chromatin organization might be able to self-reconstruct transgenerationally. We also found that the location of “chromatin organization” and “metabolic” genes is biased similarly in mouse and human genomes, suggesting that exposure to environmental stressors in different species could elicit similar phenotypic effects via self-reconstruction of disrupted chromatin organization.

Tributyltin exposure disturbs hepatic glucose metabolism in male mice

Some previous studies showed that organotin compounds induced diabetes in animal models. The underlying mechanisms should be further revealed. In this study, male KM mice were exposed to tributyltin (TBT) at 0.5, 5 and 50 μg/kg once every three days for 45 days. The TBT-treated mice exhibited an elevation of fasting blood glucose level and glucose intolerance. The fasting serum insulin levels were increased and reached a significant difference in the 50 μg/kg group; the glucagon levels were significantly decreased in all the treatments. Pancreatic β-cell mass was significantly decreased in all the treatments; α-cell mass showed a significant decrease in the 5 and 50 ug/kg groups. The transcription of pancreatic insulin gene (Ins2) showed an up-regulation and reached a significant difference in the 5 and 50 μg/kg groups, which would be responsible for the increased serum insulin levels. The transcription of glucagon gene (Gcg) in the pancreas was significantly down-regulated in the 5 and 50 ug/kg groups. The protein expression of hepatic glucagon receptor was down-regulated, while the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase was up-regulated accompanied by increased hepatic glycogen content. These results indicated that hepatic gluconeogenesis was enhanced during insulin resistance stage caused by TBT exposure, which would exert a potential risk inducing the development of diabetes mellitus.

Size, season and origin of gastropods matter in imposex assessments

Through controlled exposure to tributyltin (TBT), the effects of season, size, and population origin were evaluated on imposex incidence in Stramonita brasiliensis. Four experiments were carried out with organisms collected from three different sites on the Brazilian coast (Torres - Rio Grande do Sul, Farol de Santa Marta - Santa Catarina, and Aracruz - Espírito Santo). S. brasiliensis were anesthetized, sexed, measured, classified by size in small (< 30 mm), medium (≥ 30 to ≤ 40 mm), or big (> 40 mm) and injected in the foot muscle with 0.5 μg g−1 of TBT. Organisms were maintained during one month in aquariums with clear marine water under controlled laboratory conditions. One month after injection, the imposex assessments showed that the population from the southeast (tropical) region was more sensitive to TBT than the population from the south of Brazil (the temperate region). A greater sensitivity in the small and medium categories was observed. Females were also more susceptible to TBT when exposed during their reproductive period. Thus, the present study highlighted the need to ensure that intrinsic biological factors related to organisms are considered in such biomonitoring studies to avoid misinterpretation of results.

Tributyltin Affects Rat Vascular Contractility Through L-Type Calcium Channels

The humans being exposed to tributyltin (TBT), through the ingestion of contaminated diet, particularly seafood, and through the ingestion of indoor dust. TBT is one of the most studied organotins and some reports demonstrated that this compound interferes with the physiology of the cardiovascular system; however, the exact mechanisms involved are still under discussion. Hence, this study aims to evaluate the effects of TBT on the vascular function. The evaluation of TBT effects on the contractility of rat aorta was performed using the organ bath technique using two different contractile agents: noradrenaline (NA) and potassium chloride (KCl). The whole-cell configuration of the patch clamp technique was performed to evaluate the TBT effects on the calcium currents of A7r5 cell line. The results demonstrate that TBT interferes with the vascular system as it elicits relaxation of the rat aorta contracted by NA or by KCl and inhibits L-type calcium currents in smooth muscle cells.

Alteration of parameters of energy metabolism and ATPase enzymatic system in juvenile common carp (Cyprinus carpio) chronically exposed to tributyltin

The effect of long-term exposure to tributyltin (TBT) on energy metabolism and adenosine triphosphatase (ATPase) enzymatic system in freshwater teleost was investigated. The impact on the parameters of energy metabolism (the content of glucose (Glu) and lactate (LA), and the activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase(LDH)) in the muscle tissue, as well as on the ATP enzymatic system (ATP content, Total-ATPase, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase) in the gill tissue of common carp was evaluated. Fish were exposed to sublethal concentrations of TBT (75, 0.75, and 7.5 µg/l) for 60 days. Based on the results, long-term exposure to TBT could lead to obvious ATP enzymatic system responses, including the decreased ATP content and Na+-K+-ATPase activity, and the increased activities of Total-ATPase and Ca2+-Mg2+-ATPase. Moreover, the parameters of energy metabolism in muscle were also regulated, such as induced indices of the levels of Glu and LA, and the activities of HK and PK, and inhibited indices of LDH activity. Shortly, the measured physiological responses in fish could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity, and could be used as potential biomarkers for monitoring the TBT pollution in the field.

Sex and site-specific trends in veined rapa whelk (Rapana venosa) tributyltin bioaccumulation: considerations for biomonitoring

The imposition of male sexual characteristics onto the female (imposex) is present in wild populations of the non-native veined rapa whelk (Rapana venosa) in Chesapeake Bay, USA but does not appear to compromise reproductive function. Cultured whelks were used to test two hypotheses: (1) Observed imposex metrics will be similar to tributyltin (TBT) water concentrations at each of three sites; (2) Male and imposex/female whelks from the same site will have similar TBT body burdens. Cultured 2-year-old whelks were transplanted to three field sites in the York River, USA at the onset of their second reproductive season. Transplant site mean TBT water concentrations ranged from 1.4 ± 0.77 to 64.2 ± 57.8 ng l−1. Imposex incidence was 100% after 28 weeks with an observed M:F:IF ratio of 81:0:92 across all sites. Imposex stages (median vas deferens scale index = 4) and reproductive output were similar across sites. The imposex severity (IS = penis length/shell length) increased with increasing TBT concentrations. The relative penis length (RPLI) and relative penis size (RPSI) indices were positively related to site-specific TBT levels. Male whelks accumulated significantly higher TBT concentrations than female whelks at the site with the highest TBT concentration. Mean TBT concentrations in whelk egg capsules were significantly higher than concentrations in male or female whelk tissue. Egg capsule deposition provides a depuration mechanism for female whelks to reduce body burden of lipophilic TBT. Sex, season and reproductive status should be considered when using gastropod bioaccumulation to monitor TBT effects.

Physiological Responses in Chinese Rare Minnow Larvae Following Exposure to Low-Dose Tributyltin.

In the present study, the antioxidant response and acetylcholinesterase (AChE) activity were measured in Chinese rare minnow larvae (Gobiocypris rarus) after exposure to tributyltin (TBT) (0, 100, 400 and 800ngL(-1)) for 7days, as well as the expression of a series of genes, including cr, aptase and prl genes involved in the ion-regulatory process and igfbp3 and gh related to growth rate. Results shows that oxidative stress was generated in fish exposed to TBT, as evidenced by elevated malondialdehyde levels and the inhibition of antioxidant parameters. The activity of acetylcholinesterase (AChE) was also inhibited in fish under higher TBT stress. Moreover, genes involved in ion regulation and growth were affected, based on the regulated transcription of the cr, atpase, gh, prl and igfbp3 genes in the treated groups. The observed effects of TBT upon antioxidant responses and altered expression of genes provides insight into the use of these molecular biomarkers in evaluating mechanisms of TBT toxicity in fish.

TBT 노출에 따른 넙치, Paralichthys olivaceus의 혈액학적 성상 및 혈장성분의 변화

Juvenile Paralichthys olivaceus (mean length , mean weight ) were exposed for 10 days to tributyltin (TBT) at various concentrations (0, 1, 2, 4 and ). Hematological parameters, such as red blood cell (RBC) count, hematocrit (Ht), and hemoglobin (Hb) concentration, were considerably decreased by high TBT concentrations. In plasma constituents, inorganic components such calcium and magnesium were also significantly altered. Plasma calcium was notably decreased, whereas plasma magnesium was increased. The enzyme components, glutamic oxalate transaminase (GOT) and glutamic pyruvate transaminase (GPT), were significantly decreased by TBT exposure. The present findings suggest that TBT exposure can cause significant alterations in hematological parameters and plasma constituents of flatfish Paralichthys olivaceus.

Transcriptomes analysis of Aeromonas molluscorum Av27 cells exposed to tributyltin (TBT): Unravelling the effects from the molecular level to the organism

Aeromonas molluscorum Av27 cells were exposed to 0, 5 and 50 μM of TBT and the respective transcriptomes were obtained by pyrosequencing. Gene Ontology revealed that exposure to 5 μM TBT results in a higher number of repressed genes in contrast with 50 μM of TBT, where the number of over-expressed genes is greater. At both TBT concentrations, higher variations in gene expression were found in the functional categories associated with enzymatic activities, transport/binding and oxidation-reduction. A number of proteins are affected by TBT, such as the acriflavin resistance protein, several transcription-related proteins, several Hsps, ABC transporters, CorA and ZntB and other outer membrane efflux proteins, all of these involved in cellular metabolic processes, important to maintain overall cell viability.Using the STRING tool, several proteins with unknown function were related with others involved in degradation processes, such as the pyoverdine chromophore biosynthetic protein, that has been described as playing a role in the Sn–C cleavage of organotins.This approach has allowed a better understanding of the molecular effects of exposure of bacterial cells to TBT. Furthermore it contributes to the knowledge of the functional genomic aspects of bacteria exposed to this pollutant. Furthermore, the transcriptomic data gathered, and now publically available, constitute a valuable resource for comparative genome analysis.

Chemometric strategy for untargeted lipidomics: Biomarker detection and identification in stressed human placental cells

A lipidomic study was developed in a human placental choriocarcinoma cell line (JEG-3) exposed to tributyltin (TBT) and to a mixture of perfluorinated chemicals (PFCs). The method was based on the application of multivariate curve resolution-alternating least squares (MCR-ALS) to data sets obtained by ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC–TOF-MS) using an untargeted approach. Lipids from exposed JEG-3 cells were solid–liquid extracted and analyzed by UHPLC–TOF-MS in full scan mode, together with control samples. Raw UHPLC–TOF-MS data of the different cell samples were subdivided into 20 distinct chromatographic windows and each window was further organized in a column-wise augmented data matrix, where data from every sample was in an individual data matrix. Then, the 20 new augmented data matrices were modeled by MCR-ALS. A total number of 86 components were resolved and a statistical comparative study of their elution profiles showed distinct responses for the lipids of exposed versus control cells, evidencing a lipidome disruption attributed to the presence of the xenobiotics. Results from one-way ANOVA followed by a multiple comparisons test and from discriminant partial least squares (PLS-DA) analysis were compared as usual strategies for the determination of potential biomarkers. Identification of 24 out of the 33 proposed biomarkers contributed to the better understanding of the effects of PFCs and TBT in the lipidome of human placental cells. Overall, this study proposes an innovative untargeted LC–MS MCR-ALS approach valid for -omic sciences such as lipidomics.

Molecular responses in digestive tract of juvenile common carp after chronic exposure to sublethal tributyltin

The effect of long-term exposure to tributyltin (TBT) on the intestine-related biochemical biomarkers in common carp was investigated in this study. Fish were exposed at sub-lethal concentrations of TBT (75ng/L, 0.75 and 7.5μg/L) for 60 days. Multiple biomarkers were measured, including digestive enzymes (trypsin, lipase and amylase), antioxidant responses (malondialdehyde (MDA) and total antioxidative capacity (T-AOC)), RNA/DNA ratio and the expression of digestive-related genes (try, lipc and amy). TBT exposure at 0.75 and 7.5μg/L led to significantly inhibited activities of all digestive enzymes. At higher concentration of TBT, oxidative stress was apparent as reflected by the significant higher MDA content in the fish intestine, associated with an inhibition of T-AOC activities. After 60 days, the RNA/DNA ratio in fish intestine was significantly lower in groups exposed to TBT at higher concentrations (0.75 and 7.5μg/L). In addition, the expression levels of try, lipc and amy in intestine of all treated fish were inhibited, even at the environmental concentration (75ng/L). Our results suggest that long-term exposure to TBT could result in different responses of intestine-related biochemical biomarkers in fish, which could be used as new potential indicators for monitoring residual TBT present in aquatic environment.

Association of placenta organotin concentrations with growth and ponderal index in 110 newborn boys from Finland during the first 18 months of life: a cohort study.

BackgroundHumans are exposed to tributyltin (TBT), previously used as an antifouling paint in ships, mainly through fish consumption. As TBT is a known obesogen, we studied the association of placenta TBT and other organotin compounds (OTCs) with ponderal index (PI) and growth during the first 18 months of life in boys.MethodsIn a prospective Finnish study, 110 placenta samples were collected from mothers of boys born in 1997–1999 with (n = 55) and without (n = 55) cryptorchidism. To account for the original study design, linear regression, weighted for sampling fractions of boys with (121/55) and without (5677/55) cryptorchidism from the total cohort, was used to study the association between placenta OTCs and children’s weight, length, growth rates and PI up to 18 months of age.ResultsPlacenta TBT concentrations were above the limit of quantification (LOQ) in 99% of the samples. However, monobutyltin (MBT), dibutyltin (DBT) and triphenyltin (TPhT) concentrations were below LOQ in 90%, 35% and 57% of samples, respectively. Placenta TBT was positively associated (p = 0.024) with weight gain during the first three months of life, but no other significant associations were observed for weight or length gain. Also, no significant associations between placenta OTC concentrations and child length, weight or PI at any time point were found.ConclusionsWe observed a trend towards higher weight gain from birth to 3 months of age with increasing placenta TBT concentration. These results should be interpreted with caution because obesogenic effects in animal experiments were seen after in-utero TBT exposures to doses that were orders of magnitude higher. Also the number of study subjects included in this study was limited.

Reponses of the Hepatic Microsomal Cytochrome P450 Monooxygenase System in Rock Bream Oplegnathus fasciatus Exposed to Tributyltin (TBT)

Abstract The study was conducted to investigate the responses of the hepatic microsomal cytochrome P450 monooxygenase system in the rock bream Oplegnathus fasciatus after chronic exposure to 0, 1, 2, 4, and 8 μg/L tributyltin (TBT) concentrations for 4 weeks. Hepatic cytochrome 450 content and ethoxyresorufin O -deethylation (EROD) activity were found to significantly increase in fish treated with the higher concentration of TBT (≥4 μg/L); however, no significant changes were observed in penthoxyresorufin O -deethylation (PROD) activity in all treated groups compared to the control group. These findings suggest that exposure to a low TBT concentration (≥4 μg/L) has the potential to induce cytochrome 450 content and EROD enzyme activity in hepatic tissue in the rock bream. Key words: Oplegnathus fasciatus , Tributyltin, Cytochrome 450, EROD, PROD Introduction Many aquatic ecosystems are faced with spatially or tem-porally alarmingly high levels of xenobiotic chemicals (Brack et al., 2002; Diez et al., 2002). Tributyltin (TBT) is a typi-cal synthetic pollutant, which was selected for investigation in this study. TBT is an organotin compound used primarily as a biocide in antifouling paints for ships, boats, and fishing nets. The use of TBT as an antifouling agent in paint has been banned for small boats and fishing nets in most countries as it has been shown to be toxic to aquatic life and is an endo-crine disrupting chemical that generates severe reproductive effects in aquatic animals (Horiguchi et al., 1994). Reproduc-tive impairment in gastropods has been reported at low TBT concentrations (Gibbs et al., 1988). TBT has been shown to induce imposex and intersex in brosobranchs (Oehlmann et al., 1998), and impaired reproductive function in fish has also been described (Mc Allister and Kime, 2003).Some studies have reported toxic effects of TBT such as morphological and functional alterations of teleost gills in aquatic media (Byrne et al., 1989; Schwaiger et al., 1992; Tsu -da et al., 1992; Wang and Huang, 1998). TBT has also been shown to markedly inhibit fish hepatic CYP and in particu-lar the isozyme cytochrome P4501A1 (CYP1A), both in vivo and vitro (Fent and Bucheli, 1994; Morcillo and Porte, 1997). The CYP1A isozyme plays a key role in the biotransformation of xenobiotic compounds, leading to either their detoxifica-tion or bioactivation, while other CYP forms are important

Rapana venosa as an indicator species for TBT exposure over decadal and seasonal scales

Imposex and decline in reproductive output in marine gastropods have been linked to tributyltin (TBT) exposure. This study describes Chesapeake Bay, USA, veined rapa whelk Rapana venosa imposex incidence and sex ratios from 1998 to 2009. Tissue TBT concentrations (ng g−1) were examined with respect to whelk sex, size, and water temperature at the time of collection, and also to egg case size, hatching success, and veliger diameter. Imposex incidence declined and population sex ratios moved closer to parity from 1998 to 2009. Observed TBT concentrations (ng g−1) were higher in James River than in Ocean View whelks with higher TBT concentrations observed in males than in females. Exponential declines in TBT concentrations from female-specific first to last clutches within a reproductive season were observed, indicating that whelks depurate TBT through egg case deposition. Egg capsule hatching success and veliger size were similar for female and imposex whelks. The R. venosa imposex levels observed in Chesapeake Bay apparently do not affect the production, release, or viability of larvae.

Imposex development in Hexaplex trunculus (Gastropoda: Caenogastropoda) involves changes in the transcription levels of the retinoid X receptor (RXR)

In order to further demonstrate that TBT-induced imposex through RXR signaling is not species-specific, Hexaplex trunculus was selected as an experimental model species. We first isolated RXR in H. trunculus, and determined gene transcription through quantitative real-time PCR in key tissues (e.g., penis/penis-forming area and central nervous system:- CNS), upon exposure to tributyltin (TBT) (5 and 50ng TBTL−1). Two months of exposure to TBT induced imposex and led to a significant increase in the severity of the phenomenon in females and an increase in male penis lengths. Exposure to TBT altered RXR gene transcription in a tissue and sex-specific manner. In the CNS, there were no significant changes in RXR gene transcription between control and TBT-exposed females. A similar trend was observed in male CNS. On the contrary, in the penis-forming area/penis of females exposed to TBT, a significant increase in RXR gene transcription was observed in the 50ng TBTL−1 group. Furthermore, a positive correlation was observed between overall female penis lengths and RXR gene transcription. In males, although a trend towards an increase in RXR gene transcription in penis was observed, differences did not reach significance. Overall, the results of the present study give further support to a local role of RXR in the penis-forming area during the development of imposex by TBT, thus suggesting a conserved function of RXR in penis formation at least within prosobranch gastropods.

Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation

Recent studies suggest that endocrine disrupting chemicals (EDCs) may form a risk factor for obesity by altering energy metabolism through epigenetic gene regulation. The goal of this study is to investigate the effects of a range of EDCs with putative obesogenic properties on global DNA methylation and adipocyte differentiation in vitro. Murine N2A and human SK-N-AS neuroblastoma cells and murine preadipocyte fibroblasts (3T3-L1) were exposed to tributyltin (TBT), diethylstilbestrol (DES), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-[p]-dioxin (TCDD), 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153), hexachlorobenzene (HCB), hexabromocyclododecane (HBCD), 2,2′,4,4′-tetrabrominated diphenyl ether (BDE-47) , perfluorinated octyl acid (PFOA) and perfluorinated octyl sulfonate (PFOS). A modest decrease in global DNA methylation was observed in N2A cells exposed to 10μM DES, BPA, TCDD, BDE-47, PCB-153 and 1μM HCB, but no changes were found in the human SK-N-AS cells. We reveal for the first time that BDE-47 increases adipocyte differentiation in a dose-dependent manner (2.5–25μM). Adipocyte differentiation was also enhanced by TBT (⩾10nM) and BPA (>10μM) and inhibited by TCDD (⩾0.1nM). The other chemicals showed either modest or no effects on adipocyte differentiation at the concentrations tested (PFOA, PFOS and HBCD at 10μM; PCB-153, 3.4μM and HCB, 1μM). This study demonstrates that selected EDCs can induce functional changes in murine adipocyte differentiation in vitro which are accompanied by decreased global DNA methylation.

An Obesogen over Time: Transgenerational Impact of Tributyltin

Vol. 121, No. 3 News | Science SelectionsOpen AccessAn Obesogen over Time: Transgenerational Impact of Tributyltin Wendee Nicole Wendee Nicole Search for more papers by this author Published:1 March 2013https://doi.org/10.1289/ehp.121-a96Cited by:2View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit The term “obesogen” describes a chemical that promotes excessive weight gain by increasing adipocyte (fat cell) size or number, changing metabolism to favor fat storage, or altering the control of appetite and satiety. Previous studies have suggested that prenatal exposure to obesogens can alter metabolism in mice and predispose multipotent mesenchymal stem cells (MSCs) to become fat cells, but whether these changes last through subsequent generations was unknown. A team of researchers investigating this question exposed pregnant mice to tributyltin (TBT) and found impacts on adipogenesis through the third generation [EHP 121(3):359–366; Chamorro-Garcia et al.].TBT, which has been used as a biocide in marine paints and in textile products such as carpets, is a persistent organic pollutant that is ubiquitous in the environment. Exposure to TBT is thought to occur through many sources, including food, house dust, and consumer products.In the current study, male offspring (i.e., the F1 generation) of mice exposed to TBT during pregnancy showed marked increases in the number and size of white fat cells and significant but less pronounced increases in the weight of white fat deposits (or “depots”) around the kidney and under the skin. The two subsequent generations (F2 and F3) also showed increases in fat cell size and number and, at the two higher TBT doses, in fat depot weight. Females showed more modest differences following TBT prenatal exposure, including both increases and decreases in cell numbers, depending on location.Once used to fight mites and fungi in carpets and other textiles, TBT has been found in house dust, which is thought to be a major source of human exposure. This dust sample—which was not tested for TBT—is made up of carpet fibers (blue), cotton fibers (green), synthetic fibers (yellow), small stones (gray), dirt particles (dark brown), skin flakes (beige), and a feather.© Eye of Science/Science SourceThe team also found that F3 animals in the TBT group showed substantially increased expression of adipogenic markers in bone marrow–derived MSCs and decreased expression of osteogenic (bone lineage) markers—in other words, the stem cell population appeared reprogrammed to create fat instead of bone. The shift was more pronounced in males in all generations, and especially in the F3 generation.When the team looked at accumulation of lipids in the livers of each generation, they found that TBT-exposed F1 males and females showed marked increases in lipid accumulation; F2 and F3 generations also showed less pronounced increases in liver lipids. The investigators also found significant increases in the expression of hepatic genes related to fat creation and storage in males and females from all three generations of mice.F1 animals were exposed to TBT as fetuses, and F2 animals were potentially exposed as germ cells within the F1 fetuses. F3 animals were not exposed to TBT, yet they exhibited signs characteristic of exposure. This is the first known study to show that prenatal exposure to low, environmentally relevant concentrations of an obesogen led to transgenerational effects on white fat volume, altered stem cell programming, and liver fat accumulation in multiple generations of mice.FiguresReferencesRelatedDetailsCited by Badr El Dine F, Nabil I and Dwedar F (2017) The effect of Tributyltin on thyroid follicular cells of adult male albino rats and the possible protective role of green tea: a toxicological, histological and biochemical study, Egyptian Journal of Forensic Sciences, 10.1186/s41935-017-0012-z, 7:1, Online publication date: 1-Dec-2017. Brtko J and Dvorak Z (2015) Triorganotin compounds - ligands for “rexinoid” inducible transcription factors: Biological effects, Toxicology Letters, 10.1016/j.toxlet.2015.02.009, 234:1, (50-58), Online publication date: 1-Apr-2015. Vol. 121, No. 3 March 2013Metrics About Article Metrics Publication History Originally published1 March 2013Published in print1 March 2013 Financial disclosuresPDF download License information 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. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.