Triphenyltin Research Articles

Organotin mixtures reveal interactions that modulate adipogenic differentiation in 3T3-L1 preadipocytes.

Organotin chemicals (butyltins and phenyltins) are the most widely used organometallic chemicals worldwide and are used in industrial applications, such as biocides and anti-fouling paints. Tributyltin (TBT) and more recently, dibutyltin (DBT) and triphenyltin (TPT) have been reported to stimulate adipogenic differentiation. Although these chemicals co-exist in the environment, their effect in combination remains unknown. We first investigated the adipogenic effect of eight organotin chemicals (monobutyltin (MBT), DBT, TBT, tetrabutyltin (TeBT), monophenyltin (MPT), diphenyltin (DPT), TPT, and tin chloride (SnCl4)) in the 3T3-L1 preadipocyte cell line in single exposures at two doses (10 and 50ng/ml). Only three out of the eight organotins induced adipogenic differentiation with TBT eliciting the strongest adipogenic differentiation (in a dose-dependent manner) followed by TPT and DBT, as demonstrated by lipid accumulation and gene expression. We then hypothesized that, in combination (TBT, DBT, and TPT), adipogenic effects will be exacerbated compared to single exposures. However, at the higher dose (50ng/ml), TBT-induced differentiation was reduced by TPT and DBT when in dual or triple combination. We tested whether TPT or DBT would interfere with adipogenic differentiation stimulated by a peroxisome proliferator-activated receptor (PPARγ) agonist (rosiglitazone) or a glucocorticoid receptor agonist (dexamethasone). Both DBT50 and TPT50 reduced rosiglitazone-, but not dexamethasone-stimulated adipogenic differentiation. In conclusion, DBT and TPT interfere with TBT's adipogenic differentiation possibly via PPARγ signaling. These findings highlight the antagonistic effects among organotins and the need to understand the effects and mechanism of action of complex organotin mixtures on adipogenic outcomes.

Toxic effects of triphenyltin on the development of zebrafish (Danio rerio) embryos

Triphenyltin (TPT) is known to be an environmental endocrine disruptor and has adverse effects on aquatic animals. In this study, zebrafish embryos were treated with three different concentrations (12.5, 25, 50 nmol/L) based on the LC50 value at 96 h post fertilization (96 hpf), after TPT exposure. The developmental phenotype and hatchability were observed and recorded. Reactive oxygen species (ROS) levels in zebrafish were detected at 72 hpf and 96 hpf using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) as a probe. The number of neutrophils after exposure was observed using transgenic zebrafish Tg (lyz: DsRed). RNA-seq analysis was used to compare the gene expression changes in zebrafish embryos at 96 hpf in the control group and 50 nmol/L TPT exposure group. The data revealed that TPT caused a delay in hatching of zebrafish embryos in a time- and dose-dependent manner, as well as causing pericardial edema, spinal curvature and melanin reduction. ROS levels in embryos exposed to TPT increased, and the number of neutrophils increased after TPT exposure to Tg (lyz: DsRed) in transgenic zebrafish. RNA-seq results were also analyzed, and KEGG enrichment analysis showed that significant differential genes were enriched in the PPAR signaling pathway (P < 0.05), and the PPAR signaling pathway mainly affected genes related to lipid metabolism. The RNA-seq results were verified using real-time fluorescence quantitative PCR (RT-qPCR). Oil red O and Nile red staining showed increased lipid accumulation after TPT exposure. These findings suggest that TPT affects the development of zebrafish embryos even at relatively low concentrations.

Triphenyltin (TPT) exposure causes SD rat liver injury via lipid metabolism disorder and ER stress revealed by transcriptome analysis

BackgroundTPT is an environmental endocrine disruptor that can interfere with endocrine function. However, whether TPT can cause damage to liver structure and function and abnormal lipid metabolism and whether it can cause ER stress is still unclear. ObjectiveTo explore the effect of TPT on liver structure, function and lipid metabolism and whether ER stress occurs. MethodsMale SD rats were divided into 4 groups: control group (Ctrl group, TPT-L group (0.5 mg/kg/d), TPT-M group (1 mg/kg/d), and TPT-H group (2 mg/kg/d). After 10 days of continuous gavage, HE staining was used to observe the morphological structure of liver tissue, serum biochemical indicators were detected, gene expression and functional enrichment analysis were performed by RNA-seq, Western Blot was used to detect the protein expression level of liver tissue, and qRT-PCR was used to detect the gene expression. ResultsAfter TPT exposure, the liver structure damaged; serum TBIL, AST and m-AST levels were significantly increased in the TPT-M group, and serum TG levels were significantly decreased in the TPT-H group. TCHO and TG in liver tissues were significantly increased; transcriptomic analysis detected 105 differential genes. Enrichment analysis showed that TPT exposure mainly affected fatty acid metabolism and drug metabolism in liver tissue, and also affected the redox process of liver tissue; the protein expression levels of PPARα, PPARγ, AMPK, RXRα, IRE1α and PERK were significantly increased after TPT exposure; the expression levels of lipid metabolism-related genes Acsl1, Elovl5, Hmgcr, Hmgcs1 and Srebf1 were significantly increased in the TPT-L group, while in the TPT-M and TPT-H groups had no significant change. ConclusionsTPT exposure can cause liver injury, lipid metabolism disorder and ER stress.

Combined effect of microplastic and triphenyltin: Insights from the gut-brain axis

Microplastics (MPs), an emerging group of pollutants, not only have direct toxic effects on aquatic organisms but also cause combined toxicity by absorbing other pollutants. Triphenyltin (TPT), one of the most widely used organotin compounds, has adverse effects on aquatic organisms. However, little is known about the combined toxicity of MPs and TPT to aquatic organisms. To investigate the individual and combined toxicity of MPs and TPT, we selected the common carp (Cyprinus carpio) for a 42-day exposure experiment. Based on the environmental concentrations in a heavily polluted area, the experimental concentrations of MPs and TPT were set at 0.5 mg L−1 and 1 μg L−1, respectively. The effects of MPs combined with TPT on the carp gut–brain axis were evaluated by detecting gut physiology and biochemical parameters, gut microbial 16S rRNA, and brain transcriptome sequencing. Our results suggest that a single TPT caused lipid metabolism disorder and a single MP induced immunosuppression in carp. When MPs were combined with TPT, the involvement of TPT amplified the immunotoxic effect induced by MPs. In this study, we also explored the gut–brain axis relationship of carp immunosuppression, providing new insights for assessing the combined toxicity of MPs and TPT. At the same time, our study provides a theoretical basis for evaluating the coexistence risk of MPs and TPT in the aquatic environment.

Characteristics, sources and health risks of organotin compounds in marine organisms from the seas adjacent to the eastern ports of China

Organotin compounds (OTCs), being widely used as antifouling coatings on ships, are defined as endocrine-disrupting chemicals by the EPA due to their harmful effects on marine organisms. The eastern coast of China has developed abundant maritime transportation and fishery industries but the associated OTC pollution can pose potential health risks. In the present study, 20 species of marine organisms (including mollusks, crustaceans and fish) were collected from the seas adjacent to the eastern ports of China and 6 OTCs (ie, tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT) and triphenyltin (TPhT), diphenyltin (DPhT) and monophenyltin (MPhT)) were analyzed using GC-MS/MS. ∑OTCs in marine organisms ranged from 0.81 to 2900 ng Sn g−1 dw with the mean of 130 ng Sn g−1 dw, being at a comparatively moderate level across the world. PhTs were the dominant pollutants with the contribution up to 51%–87%. Spatially, the highest concentration of OTCs occurred in marine organisms from the ports in the Southeast Coast, and mollusks were more likely to accumulate OTCs than other species. BT concentrations in seafood decreased significantly after the implementation and enforcement of the TBT ban. The source analysis showed that BTs detected in current biota are mainly from historical exposure to antifouling coating on ships. However, PhTs may be closely associated with coastal aquaculture as well as terrestrial agriculture-related activities. The commercially important fishes were recovered a higher level of ∑OTCs than others suggesting a potential risk for protein uptake. Health risks via seafood consumption caused by OTCs were not high but children are exposed to the highest risk, followed by adolescents and adults respectively. In the future, continuous monitoring of OTCs, especially PhTs, in marine organisms from the eastern ports of China is still necessary, and effective measures to protect marine ecosystems and human health need to be taken.

Systematic toxicological analysis of the effect of salinity on the physiological stress induced by triphenyltin in Nile tilapia

Triphenyltin (TPT), a synthetic chemical, is prevalent in complex salinity areas, including estuaries and coastal regions. However, current studies on the toxicological effects of TPT relevant to the environment at different salinities are limited. In the study, biochemical, histological, and transcriptional analyses of TPT and salinity alone, or in combination, was performed on the Nile tilapia (Oreochromis niloticus) liver. Nile tilapia exhibited weakened antioxidant defenses and liver damage. Transcriptomic analysis revealed that TPT exposure primarily affected lipid metabolism and immunity; salinity exposure alone particularly affected carbohydrate metabolism; combined exposure primarily immune- and metabolic-related signaling pathways. In addition, the single exposure to TPT or salinity induced inflammatory responses by up-regulating the expression of pro-inflammatory cytokines, whereas combined exposure suppressed inflammation by down-regulating pro-inflammatory cytokine levels. These findings are beneficial to understand the negative effects of TPT exposure in Nile tilapia in the broad salinity zones and its potential defense mechanisms.

An integrative investigation of developmental toxicities induced by triphenyltin in a larval coral reef fish, Amphiprion ocellaris

Triphenyltin (TPT) is widely distributed on coastlines, which makes coral reef fish a potential target of TPT pollution. However, the negative effects of TPT on coral reef fish remain poorly understood. Therefore, in the present study, the larval coral reef fish Amphiprion ocellaris was used to investigate the developmental toxicities of TPT at environmentally relevant concentrations (0, 1, 10 and 100 ng/L). After TPT exposure for 14 d, the cumulative mortality increased, and growth was suppressed. In addition, TPT exposure inhibited the development of melanophores and xanthophores and delayed white strip formation, which might be responsible for the disruption of the genes (erbb3b, mitfa, kit, xdh, tyr, oca2, itk and trim33) related to pigmentation. TPT exposure also attenuated ossification of head skeletal elements and the vertebral column and inhibited the expression of genes (bmp2, bmp4 and sp7) related to skeletal development. The observed developmental toxicities on growth, pigmentation and skeleton development might be associated with the disruption of thyroid hormones and the genes related to thyroid hormone regulation (tshβ, thrα, thrβ, tg, tpo, dio2, and ttr). In addition, TPT exposure interfered with locomotor and shoaling behavior, and the related genes dbh, avp and avpr1aa. Taken together, our results suggest that TPT pollution might threaten the development of one of the most iconic coral reef fish, which might produce disastrous consequences on the health of coral reef ecosystems.

Organotin Antifouling Compounds and Sex-Steroid Nuclear Receptor Perturbation: Some Structural Insights.

Organotin compounds (OTCs) are a commercially important group of organometallic compounds of tin used globally as polyvinyl chloride stabilizers and marine antifouling biocides. Worldwide use of OTCs has resulted in their ubiquitous presence in ecosystems across all the continents. OTCs have metabolic and endocrine disrupting effects in marine and terrestrial organisms. Thus, harmful OTCs (tributyltin) have been banned by the International Convention on the Control of Harmful Antifouling Systems since 2008. However, continued manufacturing by non-member countries poses a substantial risk for animal and human health. In this study, structural binding of common commercial OTCs, tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPT), diphenyltin (DPT), monophenyltin (MPT), and azocyclotin (ACT) against sex-steroid nuclear receptors, androgen receptor (AR), and estrogen receptors (ERα, ERβ) was performed using molecular docking and MD simulation. TBT, DBT, DPT, and MPT bound deep within the binding sites of AR, ERα, and Erβ, showing good dock score, binding energy and dissociation constants that were comparable to bound native ligands, testosterone and estradiol. The stability of docking complex was shown by MD simulation of organotin/receptor complex with RMSD, RMSF, Rg, and SASA plots showing stable interaction, low deviation, and compactness of the complex. A high commonality (50-100%) of interacting residues of ERα and ERβ for the docked ligands and bound native ligand (estradiol) indicated that the organotin compounds bound in the same binding site of the receptor as the native ligand. The results suggested that organotins may interfere with the natural steroid/receptor binding and perturb steroid signaling.

Synthesis, Characterization, and Comparison of Disinfectant Bioactivity Test of Two Triphenyltin(IV) Compounds

This paper aims to report the synthesis of two new organotin(IV) carboxylate derivatives, triphenyltin(IV) 4-aminobenzoate (2) and triphenyltin(IV) 4-nitrobenzoate (3) and to examine their antibacterial activity as a disinfectant. These compounds were prepared by reacting triphenyltin(IV) hydroxide (1) with 4-aminobenzoic acid and 4-nitrobenzoic acid, respectively. Compound (2) was obtained as a yellow solid with a yield of 84.09% and compound (3) in the form of a white solid with a yield of 80.70%. These compounds were well characterized using UV-Vis spectrometry, FT-IR spectrometry and NMR spectroscopy. The bioactivity test as a disinfectant was tested against Salmonella typhosa and Staphylococcus aureus. The activity test was carried out by measuring the optical density (OD) of the tested compounds with concentration variations of 5x10-3, 1x10-3, and 5x10-4 M in methanol and 5% dimethyl sulfoxide (DMSO), commercial Wipol (2.5% pine oil) was used as a positive control with observations monitored at contact times of 0, 5, 10, and 15 minutes. The results showed that of both compounds were active against the two bacteria compared to the positive control with compound 3 found to be more active than compound 2.

Assessing the ecotoxicity of combined exposure to triphenyltin and norfloxacin at environmental levels: A case study of immunotoxicity and metabolic regulation in carp (Cyprinus carpio)

This paper evaluates the coexistence risks of triphenyltin (TPT) and norfloxacin (NOR) to aquatic organisms in the aquatic environment. Carp (Cyprinus carpio) was used as the test organism, the control and exposure groups (1 μg/L TPT), 1 mg/L (NOR), 1 μg/LTPT+1 mg/LNOR (TPT_NOR)) were set up according to the environmental concentration in the severely polluted area for 42 days. The single/combined toxic effects of TPT and NOR on aquatic organisms were evaluated by analyzing carp brain transcriptome sequencing, gut microbiota structure, and detection of biochemical indicators and RT-qPCR. Our results show that TPT and NOR induce lipid metabolism disorder in carp brain tissue, affecting the metabolism of cytochrome P450 to exogenous substances, and NOR also induces immunosuppression in carp. Long-term exposure to TPT combined with NOR amplifies the monotoxicity of TPT or NOR on lipid metabolism and immunosuppression in carp, induces immune dysfunction in brain tissue and changes in gut microbiota structure. However, TPT_NOR has no obvious neurotoxicity on the brain, but it can inhibit the level of intestinal MDA. This highlights that co-exposure of TPT and NOR amplifies metabolic disorders and immunosuppressive functions in carp.

Physiological responses of marine Chlorella sp. exposed to environmental levels of triphenyltin.

Triphenyltin (TPT) is a herbicide and antifouling agent that has been widely used. After TPT flows into water bodies, it will cause toxic effects on marine life. We evaluated the effect of environmental concentration level (0, 10, 100, and 200ng/L) on the cell density, antioxidant capability, and photosynthesis-related genes in the marine Chlorella sp. The results showed that 10 and 100ng/L TPT can promote the growth of marine Chlorella sp., 200ng/L TPT can inhibit the growth of marine Chlorella sp., and the TPT toxicity was accumulative. The chlorophyll composition changed. The content of chlorophyll a in 100ng/L and 200ng/L groups was significantly higher than that in the control group (p < 0.05) in 13days. The content of chlorophyll b in the 100ng/L and 200ng/L groups in 1day and 13days was significantly different from that in the control group (p < 0.05). The content of total chlorophyll in the 100ng/L and 200ng/L groups in 13days was higher than that in the control group (p < 0.05). The 200ng/L group began to suffer oxidative damage on the 12th day, and the pigment protein complex responded to oxidative damage through self-feedback regulation. On the 18th day, chld, cao, psy, rbcS, and rbcL genes were downregulated, and psbA gene was upregulated in the 10ng/L and 100ng/L groups, which may be a feedback regulation of self-oxidative damage. This paper analyzed toxicity of environmental levels of TPT to marine Chlorella sp., which provided new data support for the comprehensive evaluation of its marine ecological toxicity.

Toxic effects of triphenyltin on the silkworm Bombyx mori as a lepidopterous insect model

Triphenyltin (TPT) is a widely used reagent in various industries and agriculture, but is also known to accumulate in natural ecosystems and animal tissues. Hence, the aim of this study was to comprehensively assess the toxicity of TPT in the silkworm Bombyx mori as a model insect. The results showed that TPT exposure for the entire 5th instar larval stage significantly reduced the weight of silkworm pupa and inhibited development of the silkworm midgut. Following exposure to 2 μg/kg of TPT for 4 days, differentially expressed genes in midgut were associated with enriched pathways involved in the metabolism of carbohydrates, lipids, and amino acids, as determined by RNA sequencing. Furthermore, the metabolic profiles of the intestinal content of silkworms exposed to 2 μg/kg of TPT for 4 days were markedly altered and differential metabolites produced by metabolism of carbohydrates, lipids, and amino acids were enriched as determined by non-targeted GC-MS/MS metabolomics. This study provides novel insights into the mechanisms underlying the toxicity of TPT and emphasizes the risks posed by such pollutants released into the environment.

Aqua-(2-formylbenzoato)triphenyltin(IV) induces cell cycle arrest and apoptosis in hypoxic triple negative breast cancer cells

Hypoxia plays a vital role in tumor microenvironment by allowing development and maintenance of cancer cells thereby led to major hindrance for effective anticancer therapy and main reason for failure of most anticancer drugs. We herein investigated the therapeutic efficacy and molecular mechanism of action of aqua-(2-formylbenzoato) triphenyltin (IV) compound (OTC) in MDA-MB-231 cell line. Cobalt chloride induced hypoxic MDA-MB-231 cells treated with OTC were used to access cytotoxicity, ROS, cellular apoptosis, and cell cycle progression. Further, expression of HIF-1α and VEGF, as well as apoptotic proteins like p53, Bax, Bcl-2 and caspase 3 were assessed. The findings indicated that OTC is more effective towards CoCl2 induced hypoxic cells when compared to normoxic cells and the results are far superior to doxorubicin. Additionally, our study revealed that OTC facilitates more ROS production induced cell cycle arrest and promote apoptosis. Furthermore, OTC significantly down regulates the expression of Hif-1α, VEGF and Bcl-2 in hypoxic condition and elevates the level of p53, Bax, cytochrome-C and Caspase 3. Our in vitro studies demonstrated that OTC showed better efficacy than doxorubicin, corroborating that OTC could be a promising compound for hypoxic cancer that also display multi drug resistant.

Concentrations of organotin compounds in aquatic biota in coastal waters of Johor, Malaysia

AbstractThe concentrations of organotin (OT) compounds, butyltin (BT) and phenyltin (PT), in aquatic organisms from Merambong and Tinggi Island, Malaysia, which differ in industrial and economic activities, were measured. Tributyltin (TBT) compounds among BTs ranged from 2.9–28 and &lt;0.1–21 ng g−1 ww in aquatic organisms from Merambong and Tinggi Island, respectively. Triphenyltin (TPT) compounds among PTs ranged from &lt;0.1–25 ng g−1 ww and &lt;0.1–61 ng g−1 ww in aquatic organisms from Merambong and Tinggi Island, respectively. A survey of OT concentrations among the species of OT compounds revealed that the concentrations of BTs and PTs in crabs and clams were high while those in fish were low. Correlation analysis with stable nitrogen isotopes suggest that OT compounds did not accumulate in aquatic organisms through the food web. The measurement of OT compounds in tissues and organs of fish revealed that BT concentrations in liver were higher than those in muscle and that BTs were detected in eggs of fish.

Physiological responses in Nile tilapia (Oreochromis niloticus) induced by combined stress of environmental salinity and triphenyltin

Triphenyltin (TPT) has attracted considerable attention owing to its vitality, bioaccumulation, and lurking damage. TPT widely exists in complex salinity areas such as estuaries and coastal regions. However, there are few studies on the toxicological behavior of TPT under different salinity. In the study, juvenile Nile tilapia (Oreochromis niloticus) were utilized as model animals to investigate the effects of environmental relevant TPT exposure on the osmoregulation and energy metabolism in gill under different salinity. The results showed that salinity and TPT single or combined exposure affected the morphology of the gill tissue. After TPT exposure, Na+-K+-ATPase (NKA) activity significantly decreased at 0 ppt, while NKA and Ca2+-Mg2+-ATPase (CMA) activities significantly increased at 15 ppt. In addition, significantly higher succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) activities were found in the control fish compared to the TPT-exposed ones at 15 ppt. Quantitative real-time PCR results showed that TPT exposure affected the expression of osmoregulation and energy metabolism-related genes under different salinity. Overall, TPT exposure interfered with osmoregulation and energy metabolism under different salinity. The study will provide reference data for assessing the toxicity of organotin compounds in complex-salinity areas.

A new perspective on endocrine disrupting effects of triphenyltin on marine medaka: From brain transcriptome, gut content metabolome and behavior

Triphenyltin (TPT) is an endocrine contaminant that is often detected in the environment. However, the mechanism of the effects of TPT on biological systems is not fully understood. Here we exposed marine medaka (Oryzias melastigma) to TPT for 21 days. Brain transcriptome, intestinal content metabolism group, and behavior analysis were carried out. Through the comprehensive analysis of multiomics for the in-depth understanding of the ways related to health improvement, we determined that the glycine-serine-threonine metabolic axis was most perturbed by TPT. Through behavioral analysis, it was found that there was behavioral hyperactivity in the exposed group; behavioral hyperactivity may be caused by the interference of TPT with the neuroendocrine system. In order to gain a full understanding of the impacts of TPT on human health, transcriptomic screening of differential genes and an impartial attitude based on bioinformatics were used. Gene-disease interaction analysis using the Comparative Toxicogenomics Database (CTD) revealed the possible effects of TPT on human health. Finally, based on these findings, the relevant adverse outcome pathway (AOP), which is the “epigenetic modification of PPARG leading to adipogenesis,” was identified from AOP Wiki. Further research is required to validate the potential AOP of TPT.

The organotin triphenyltin disrupts cholesterol signaling in mammalian ovarian steroidogenic cells through a combination of LXR and RXR modulation

Organotins, a chemical family with over 30 congeners to which humans are directly exposed to through food consumption, are a chemical class widely used as stabilizers in polyvinyl chloride, and biocides in antifouling products. Aside from tributyltin (TBT), toxicological information on other organotin congeners, such as triphenyltin (TPT), remains scarce. Our previous work has demonstrated that TBT can interfere with cholesterol trafficking in steroidogenic cells. Given their structural similarities, we hypothesized that TPT, similar to TBT, disrupts intracellular cholesterol transport and impairs steroidogenesis in ovarian theca cells. To test this, human and ovine primary ovarian theca cells were isolated, purified and exposed to TPT at environmentally relevant doses (1 or 10 ng/ml) in pre-luteinized (48 h exposure) or luteinizing cells (72 h exposure). Intracellular cholesterol levels, progesterone, and testosterone secretion and gene expression of nuclear receptors, cholesterol transporters, and steroidogenic enzymes were evaluated. In ovine cells, TPT upregulated StAR, ABCA1, and SREBF1 mRNA and ABCA1 protein in both pre-luteinized and luteinized stages. TPT did not alter intracellular cholesterol or testosterone synthesis, but upregulated progesterone production. Inhibitor and shRNA knockdown approaches were then used to evaluate the role of retinoid X receptor (RXR) and liver X receptor (LXR) on TPT's effects. TPT upregulated ABCA1 and StAR expression was blocked by both LXR and RXR antagonists. TPT's effect on ABCA1 expression was reduced in LXRβ and RXRβ knockdown theca cells. Similar findings were obtained with primary human theca cells. No synergistic effect of TBT and TPT was observed. In conclusion, at an environmentally relevant dose, TPT upregulates theca cell cholesterol transporter ABCA1 expression via RXR and LXR pathways. Similar effects of TPT on human and sheep theca cells supports its conserved mechanism across mammalian theca cells.

Triphenyltin disrupts the testicular microenvironment and reduces sperm quality in adult male rats.

Triphenyltin (TPT) is organotin that is widely used as an anti-fouling agent and has been determined to have male reproductive toxicity. The objective of this study was to investigate the effects of TPT on the testicular microenvironment and sperm quality in male rats. Adult male Sprague Dawley rats were daily gavaged with TPT (0, 0.5, 1, and 2mg/kg body weight) for 28 days. The results showed that TPT dose-dependently decreased sperm count and sperm motility, interfered with sperm histone-protamine replacement process, and significantly increased sperm deformity rate, but did not affect sperm DNA integrity. TPT at 2mg/kg significantly decreased the gene and protein expressions of testis PCNA and Ki67, and dose-dependently decreased the number of PCNA-positive cells and Ki67-positive cells. TPT at 1mg/kg and/or 2mg/kg down-regulated the expression of StAR, SF1, P450scc, FSHR, WT1, DDX4 and PLZF, and up-regulated SOX9 expression. Simultaneously, TPT reduced serum testosterone levels at each dose and dose-dependently decreased the expression of Leydig cells regulators (INSL3, IGF1, inhibin B) and Sertoli cells regulators (GDNF, FGF2, CXCL12, ETV5), altered testicular microenvironment. Further, in vitro, we treated TM3 (Leydig cells), TM4 (Sertoli cells) and GC-1 (spermatogonia) cells with 1-100nM TPT for 24h. 100nM TPT significantly down-regulated the expression of the above indicators in TM3 and TM4 cells but did not directly affect the cell proliferation ability of GC-1. However, after co-culturing TPT-treated TM3 or TM4 cells with GC-1cells, it was found that TPT-treated TM3 or TM4 cells dose-dependently reduced the gene and protein expression levels of PCNA and Ki67 and increased cytotoxicity in GC-1cells. In conclusion, TPT impairs the proliferative ability of spermatogonia by disrupting the microenvironment of Leydig cells and Sertoli cells, which in turn leads to low sperm quality in adult male rats.

Triphenyltin exposure induced abnormal morphological colouration in adult male guppies (Poecilia reticulata)

Fish morphological colouration is essential for their survival and reproduction success; however, it is vulnerable to environmental factors, such as pollutants. Triphenyltin (TPT) is widespread in aquatic ecosystems, and its impacts on fish have been problematic. Therefore, the purpose of this study was to investigate the effects of TPT at environment-related concentrations (0, 1, 10 and 100 ng Sn/L) on morphological colouration in male guppies (Poecilia reticulata). The results showed that TPT exposure affected both orange/red and dark morphological colouration in guppies. The faded orange/red colouration might be related to the decrease of coloured pteridine and Pts (6-Pyruvoyltetrahydropterin Synthase) expression. In addition, TPT exposure induced melanogenesis, however, much melanin was distributed diffusely in the skin and did not seem to form a spot pattern, giving the fish a dull appearance. According to the skin transcriptional profiles, the changes of dark morphological colouration might be related to the changes in genes related to the functions of melanosome components (Gpnmb, Slc45a2 and Tyr), construction (Ap3d1, Fig4, Hps3, Hps5, Lyst, Rabggta, Txndc5 and Vps33a), and transport (Rab27a). Additionally, genes related to the regulation of melanogenesis (Atrn and Pomc) and system effects (Atox1, Atp6ap2, Atp6v1f, Atp6v1h, Rpl24, Rps19 and Rps20) might also be involved in the molecular mechanisms of abnormal morphological colouration induced by TPT. The present study provides crucial data on the molecular basis of abnormal morphological colouration in fish exposed to TPT and underscores the importance of toxicological studies of the effects of pollutants in aquatic environments on fish morphological colouration.

Organotins in a food web from the Three Gorges Reservoir, China: Trophic enrichment and potential health risk

Triphenyltin (TPhT) and tributyltin (TBT) remain widely present in various aquatic environments despite restrictions on their use in many countries for many years. The biomagnification of these compounds in the aquatic food web remains controversial. This study reports the bioaccumulation of TPhT and TBT in aquatic animals in the Three Gorges Reservoir (TGR), a deep-water river channel-type reservoir and the largest reservoir in China. We measured TPhT, TBT and their metabolites in 2 invertebrates, 27 fish and the aquatic environment. The logarithmic bioaccumulation factors of TPhT and TBT were 4.37 and 3.77, respectively, indicating that TPhT and TBT were enriched in organisms of the TGR. Both TPhT and TBT concentrations were significantly and positively correlated with trophic level, with trophic magnification factors of 3.71 and 3.63, respectively, indicating that TPhT and TBT exhibited similar trophic enrichment in the freshwater food web of the TGR. The results of health risk assessment showed that although all hazard index (HI) values were <1, more attention should be paid to the health risk to children associated with consumption of aquatic products (HI = 0.67). This study provides powerful evidence of trophic enrichment of TPhT and TBT in a freshwater food web in a deep-water river channel-type reservoir and provides valuable data regarding organotins in aquatic animals in the TGR.