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Bioencrustation is a natural process resulting from the colonisation and growth of organisms on solid substrates. For more than 40 years, Tributyltin (TBT) has been used as a biocide in antifouling paint. Since microalgae are constantly exposed to TBT, the growth of two microalgae species of the Guanabara Bay (Tetraselmis sp. and Chattonella subsalsa) was analysed in the present study. For this, the microalgae were grown using f/2 medium; potassium dichromate was used to guarantee the validity of the used method. To assess the effects on both genera of microalgae, different concentrations of TBT (ranging from 0.1 to 50 ng.L−1 diluted in f/2 medium) were used. All tests were carried out under a germination chamber, and the cell density was measured after 96 h. The results indicated that concentrations below 4.2 ng.L−1 were sufficient to inhibit 50% of the microalgae growth, demonstrating TBT can still be toxic even in ultra-low concentrations. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT), a common organotin environmental pollutant, may pose a threat to human development during critical early-life periods. We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid (FA). Specifically, after early-life exposure (1–21 days post-fertilization, dpf) to TBT (0, 1, 10 and 100 ng/L), zebrafish (Danio rerio) were cultured in clean medium until sexual maturity. The exposed females were mated with unexposed males to produce embryos (F1). The F1 generation were cultured (4–120 hours post-fertilization, hpf) with and without 1 mmol/L FA. The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring (F1) were significantly enhanced anxiety and reduced aggression, decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body. Moreover, the intergenerational neurodevelopmental toxicity, as manifested in the F1 generation, was attenuated by FA supplementation. In summary, early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish, and DNA methyl donors had a protective effect on F1 neurodevelopment, which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants. [Display omitted] [ABSTRACT FROM AUTHOR]

Combining biologically active compounds with nanocarriers is an emerging and promising strategy for enhancing the activities of molecules while reducing their levels of toxicity. Green nanomaterials have recently gained momentum in developing protocols for treating and preserving artifacts. In this study, we designed a functional biohybrid material by incorporating tributyltin(IV) ferulate (TBT-F) into halloysite nanotubes (HNTs), generating a new formulation called HNT/TBT-F. The primary objective was to develop a formulation with robust antimicrobial properties and reinforcing features for treating paper with artistic and historical value. To characterize HNT/TBT-F, assess the HNT's loading capacity, and investigate the TBT-F release kinetics from the nanotubes, various analytical techniques, including UV-Vis and infrared spectroscopies, thermogravimetry, and microscopy analysis, were employed. Furthermore, we evaluated the antimicrobial potential of TBT-F and HNT/TBT-F against Kocuria rhizophila, a bacterial strain known for its opportunistic behavior and a cause of artifact biodeterioration. HNT/TBT-F exhibited a significantly stronger bactericidal effect than TBT-F alone against K. rhizophila cells growing planktonically or those forming a biofilm. This enhanced performance could relate to the confinement of TBT-F within the nanotubes, which likely improved its physical-chemical stability and increased the local concentration of TBT-F upon contact with the bacterial cells. Additionally, we evaluated the mechanical properties of a paper treated with HNT/TBT-F, assessing any potential alterations in its color. The findings of this study highlight the favorable attributes of the HNT/TBT-F formulation and its potential for developing protocols aimed at consolidating and preserving culturally significant paper objects. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, the toxicity of tributyltin (TBT) was investigated. Sea urchins (Hemicentrotus pulcherrimus) were used as the experimental animals, and the embryonic toxicity of TBT was investigated by observing the fertilization and embryonic development rates of germ cells exposed to TBT. The fertilization rate exhibited decreasing trends as the concentration of TBT increased. Embryo development was delayed as the TBT concentration increased. Embryos whose development was delayed following TBT exposure progressed well when shifted to fresh media without TBT. The results showed that TBT had a negative effect on embryonic development. Embryonic development was restored on removal of TBT exposure. This result has important implications from the perspective of restoring polluted ecosystems. In this study, gametotoxicity and embryotoxicity experiments were performed using Hemicentrotus pulcherrimus to investigate the toxic effects of tributyltin (TBT). The effects of TBT on fertilization and embryogenesis were assessed at various concentrations (0, 0.02, 0.05, 0.09, 0.16, 0.43, 0.73, 4.68, and 9.22 ppb). The fertilization rates decreased in a concentration-dependent manner, with significant reduction following treatment with TBT at 0.05 ppb. Embryos exhibited developmental impairment after TBT exposure at each tested concentration. The frequency of developmental inhibition delay that treatment with TBT delayed embryonic development in a dose-dependent manner, with 100% of embryos exhibiting developmental impairment at 4.68 ppb. During developmental recovery tests, embryos cultured in fresh media without TBT showed advanced embryonic development. Although the observed normal development after transferring the developmentally delayed embryos to fresh media without TBT offers prospects for the restoration of contaminated environments, embryonic development remained incomplete. These results suggest that TBT adversely affects the early embryonic development of H. pulcherrimus. [ABSTRACT FROM AUTHOR]

Tributyltin is used in industrial applications. This current research aimed to study the effect of Tributyltin on the thyroid gland structure and function of adult male albino rats and the protective effect of Lycopene. Twenty-one male adult albino rats were classified into three groups: Control, treated that received Tributyltin, and protective that received Lycopene with Tributyltin. At the end of the experiment, blood samples were collected and T4, T3, and (TSH) were measured. Tissue superoxide dismutase (SOD) and malondialdehyde (MDA) were estimated. Thyroid gland specimens were processed for histological and immunohistochemical examination. Then morphometric and statistical analyses were done. The treated group showed affection in thyroid function and histological structure as vacuolated colloid and cytoplasm and dark nuclei. Ultrastructurally, follicular cells showed irregular shrunken nuclei, atrophied apical microvilli, vacuoles, multiple lysosomal granules, mitochondria with destructed cristae, and extensively dilated rough endoplasmic reticulum. There was increase in Caspase-3 immunoexpression and decrease in Beclin-1 immunoexpression. The thyroid structure and biochemical markers improved after Lycopene administration. The thyroid gland damage caused by Tributyltin is ameliorated by Lycopene. [ABSTRACT FROM AUTHOR]

This study was performed to explore in detail the toxic effects of Tributyltin Chloride (TBT) on the pituitary-testicular axis and the possible amelioration with Hesperidin. Seventy-two adult male albino rats were divided into four groups: Control group (I), TBT-treated group (II), TBT+Hesperidin group (III), and Recovery group (IV). Body and testicular weights were measured. Blood samples were taken to estimate serum levels of testosterone, FSH and LH hormones by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) level was measured in testes homogenates. Tissue samples from the pituitary glands and testes were processed for light, electron microscope examination, and immunohistochemical detection of anti-FSH, and Ki67 proteins. Results showed a statistically significant decrease in testicular weight, serum testosterone, FSH and LH levels and a significant increase in tissue MDA in the TBT group when compared to the control group. TBT treatment caused severe histopathological changes with decreased area percent of PAS-stained basophils, and anti FSH immuno-stained gonadotrophs in the pituitary gland. The testes of group II also showed marked tissue damage, cell loss with decreased epithelial height and decreased number of proliferating spermatogenic cells. Hesperidin supplementation with TBT proved significant amelioration of the previously mentioned parameters in both glands which could improve male fertility. In conclusion: The flavonoid Hesperidin has the potential to protect against the reproductive damage induced by TBT in susceptible individuals. [ABSTRACT FROM AUTHOR]

Metal-derived platinum complexes are widely used to treat solid tumors. However, systemic toxicity and tumor resistance to these drugs encourage further research into similarly effective compounds. Among others, organotin compounds have been shown to inhibit cell growth and induce cell death and autophagy. Nevertheless, the impact of the ligand structure and mechanisms involved in the toxicity of organotin compounds have not been clarified. In the present study, the biological activities of commercially available bis(tributyltin) oxide and tributyltin chloride, in comparison to those of specially synthesized tributyltin trifluoroacetate (TBT-OCOCF3) and of cisplatin, were assessed using cells with different levels of tumorigenicity. The results show that tributyltins were more cytotoxic than cisplatin in all the tested cell lines. NMR revealed that this was not related to the interaction with DNA but to the inhibition of glucose uptake into the cells. Moreover, highly tumorigenic cells were less susceptible than nontumorigenic cells to the nonunique pattern of death induced by TBT-OCOCF3. Nevertheless, tumorigenic cells became sensitive when cotreated with wortmannin and TBT-OCOCF3, although no concomitant induction of autophagy by the compound was detected. Thus, TBT-OCOCF3 might be the prototype of a family of potential anticancer agents. [ABSTRACT FROM AUTHOR]

The nuclear receptor, constitutive androstane receptor (CAR), which forms a heterodimer with the retinoid X receptor (RXR), was initially reported as a transcription factor that regulates hepatic genes involved in detoxication and energy metabolism. Different studies have shown that CAR activation results in metabolic disorders, including non-alcoholic fatty liver disease, by activating lipogenesis in the liver. Our objective was to determine whether synergistic activations of the CAR/RXR heterodimer could occur in vivo as described in vitro by other authors, and to assess the metabolic consequences. For this purpose, six pesticides, ligands of CAR, were selected, and Tri-butyl-tin (TBT) was used as an RXR agonist. In mice, CAR's synergic activation was induced by dieldrin associated with TBT, and combined effects were induced by propiconazole, bifenox, boscalid, and bupirimate. Moreover, a steatosis, characterized by increased triglycerides, was observed when TBT was combined with dieldrin, propiconazole, bifenox, boscalid, and bupirimate. Metabolic disruption appeared in the form of increased cholesterol and lowered free fatty acid plasma levels. An in-depth analysis revealed increased expression of genes involved in lipid synthesis and lipid import. These results contribute to the growing understanding of how environmental contaminants can influence nuclear receptor activity and associated health risks. [ABSTRACT FROM AUTHOR]

Protodenitration, a direct reduction of nitroalkanes to corresponding alkanes, already spans two centuries and is enabled by various reagents. This mini‐review provides a historical development of the fundamental transformation and highlights the governing position of the Ono‐Tanner reaction employing tributyltin hydride. Due to the unchallenged dominance of the toxic tributyltin hydride and environmentally unpopular solvents sharply contrasting with modern ecological trends, the current situation was dubbed "the last fortress of tin's tyranny." [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is an environmental chemical, which was used as an antifouling agent for ships. Although its use has been banned, it is still persistently present in ocean sediments. Although TBT reportedly causes various toxicity in mammals, few studies on the mechanisms of biological response against TBT toxicity exist. The well-established Keap1-Nrf2 pathway is activated as a cytopro-tective mechanism under stressful conditions. The relationship between TBT and the Keap1-Nrf2 pathway remains unclear. In the present study, we evaluated the effect of TBT on the Keap1-Nrf2 pathway. TBT reduced Keap1 protein expression in Neuro2a cells, a mouse neuroblastoma cell line, after 6 hr without altering mRNA expression levels. TBT also promoted the nuclear translocation of Nrf2, a transcription factor for antioxidant proteins, after 12 hr and augmented the expression of heme oxygenase 1, a downstream protein of Nrf2. Furthermore, TBT decreased Keap1 levels in mouse embryonic fibroblast (MEF) cells, with the knockout of Atg5, which is essential for macroautophagy, as well as in wild-type MEF cells. These results suggest that TBT activates the Keap1-Nrf2 pathway via the reduction in the Keap1 protein level in a macroautophagy-independent manner. The Keap1-Nrf2 pathway is activated by conformational changes in Keap1 induced by reactive oxygen species or electrophiles. Furthermore, any unutilized Keap1 protein is degraded by macroautophagy. Understanding the novel mechanism governing the mac-roautophagy-independent reduction in Keap1 by TBT may provide insights into the unresolved biological response mechanism against TBT toxicity and the activation mechanism of the Keap1-Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is an obesogenic endocrine disrupting chemical (EDC) linked with several metabolic complications. Brown adipose tissue (BAT) is the principal site for thermogenesis, making it a potential target for obesity management and metabolic disease. However, few studies have evaluated TBT effect on BAT function. In this investigation, we assessed whether subacute (15 days) and low dose of TBT exposure (100 ng/kg/day) results in abnormal BAT morphophysiology in adult male rats. Body temperature, BAT morphology, inflammation, oxidative stress, collagen deposition and BAT metabolic gene expression markers were assessed in room temperature (Room, ∼24 ºC) and after cold tolerance test (Cold, ∼4 ºC) conditions. A reduction in body temperature was observed in both Room and Cold conditions in TBT rats, suggesting abnormal BAT thermogenic function. Changes in BAT morphology were observed in TBT rats, with an increase in BAT lipid accumulation, an increase in BAT unilocular adipocyte number and a decrease in BAT multilocular adipocyte number in Room condition. All these parameters were opposite in Cold condition TBT rats, leading to a borderline increase in BAT UCP1 protein expression. An increase in BAT mast cell number was observed in TBT rats in Room condition. An increase in ED1 protein expression (macrophage marker) was observed in TBT rats in Cold condition. Oxidative stress and collagen deposition increased in both Room and Cold conditions in TBT rats. TBT exposure caused a borderline increase in BAT COL1A1 protein expression in Cold condition. Further, strong negative correlations were observed between body temperature and BAT lipid accumulation, and BAT lipid accumulation and multilocular adipocyte number. Thus, these data suggest that TBT exposure impaired BAT morphophysiology through impacts on lipid accumulation, inflammation, fibrosis and oxidative stress in male rats. [Display omitted] • TBT exposure impairs thermogenic function. • TBT exposure led to BAT lipid accumulation. • TBT exposure led to BAT inflammation. • TBT exposure led to BAT oxidative stress. • TBT exposure led to BAT fibrosis. [ABSTRACT FROM AUTHOR]

We describe here a simple protocol yielding small (<2 nm) crystalline Pd2Sn nanoparticles (NPs) along with Pd homologues for sake of comparison. These NPs were obtained via an organometallic approach using Pd2(dba)3·dba (dba = dibenzylideneacetone) in THF with 2 equivalents of tributyltin hydride under 4 bars of H2 at room temperature. The Pd NP homologues were prepared similarly, using Pd2(dba)3·dba with 2 equivalents of n-octylsilane. These NPs were found to be crystalline and very small with a similar mean size (ca. 1.5 nm). These NPs were finally used as nanocatalysts in solution for a benchmark Suzuki–Miyaura cross-coupling reaction. The Pd2Sn NPs were found to be more active than Pd NPs analogues, exhibiting remarkable performances with Pd loading as low as 13 ppb. This result demonstrates a beneficial effect of tin on palladium in catalysis. [ABSTRACT FROM AUTHOR]

Tri-Butyl Tin (TBT) remains as a legacy pollutant in the benthic environments. Although the toxic impacts and endocrine disruption caused by TBT to gastropod molluscs have been established, the changes in energy reserves allocated to maintenance, growth, reproduction and survival of European oysters Ostrea edulis, a target species of concerted benthic habitat restoration projects, have not been explored. This study was designed to evaluate the effect of TBT chloride (TBTCl) on potential ions and relevant metabolomic pathways and its association with changes in physiological, biochemical and reproductive parameters in O. edulis exposed to environmental relevant concentrations of TBTCl. Oysters were exposed to TBTCl 20 ng/L (n = 30), 200 ng/L (n = 30) and 2000 ng/L (n = 30) for nine weeks. At the end of the exposure, gametogenic stage, sex, energy reserve content and metabolomic profiling analysis were conducted to elucidate the metabolic alterations that occur in individuals exposed to those compounds. Metabolite analysis showed significant changes in the digestive gland biochemistry in oysters exposed to TBTCl, decreasing tissue ATP concentrations through a combination of the disruption of the TCA cycle and other important molecular pathways involved in homeostasis, mitochondrial metabolism and antioxidant response. TBTCl exposure increased mortality and caused changes in the gametogenesis with cycle arrest in stages G0 and G1. Sex determination was affected by TBTCl exposure, increasing the proportion of oysters identified as males in O. edulis treated at 20ng/l TBTCl, and with an increased proportion of inactive stages in oysters treated with 2000 ng/l TBTCl. The presence and persistence of environmental pollutants, such as TBT, could represent an additional threat to the declining O. edulis populations and related taxa around the world, by increasing mortality, changing reproductive maturation, and disrupting metabolism. Our findings identify the need to consider additional factors (e.g. legacy pollution) when identifying coastal locations for shellfish restoration. [ABSTRACT FROM AUTHOR]

The obesity epidemic is considered a global public health crisis, with an increase in caloric intake, sedentary lifestyles and/or genetic predispositions as contributing factors. Although the positive energy balance is one of the most significant causes of obesity, recent research has linked early exposure to Endocrine-Disrupting Chemicals (EDCs) such as the obesogen tributyltin (TBT) to the disease epidemic. In addition to their actions on the hormonal profile, EDCs can induce long-term changes in gene expression, possibly due to changes in epigenetic patterns. Long non-coding RNAs (lncRNAs) are epigenetic mediators that play important regulatory roles in several biological processes, through regulation of gene transcription and/or translation. In this study, we explored the differential expression of lncRNAs in gonadal white adipose tissue samples from adult male C57BL/6J F4 generation, female C57BL/6J offspring exposed (F0 generation) to 50 nM TBT or 0.1% DMSO (control of vehicle) via drinking water provided during pregnancy and lactation, analyzing RNA-seq data from a publicly available dataset (GSE105051). A total of 74 lncRNAs were differentially expressed (DE), 22 were up-regulated and 52 were down-regulated in the group whose F4 ancestor was exposed in utero to 50nM TBT when compared to those exposed to 0.1% DMSO (control). Regulation of DE lncRNAs and their potential partner genes in gonadal white adipose tissue of mice ancestrally exposed to EDC TBT may be related to the control of adipogenesis, as pathway enrichment analyses showed that these gene partners are mainly involved in the metabolism of lipids and glucose and in insulin-related pathways, which are essential for obesity onset and control. [ABSTRACT FROM AUTHOR]

Environmental contaminant exposures occur due to the widespread use of synthetic chemicals. Tributyltin (TBT), dibutyltin (DBT), and pentachlorophenol (PCP) are each used in a variety of applications, including antifouling paints and stabilizers in certain plastics. Each of these compounds has been found in human blood, as well as other tissues, and they have been shown to stimulate pro-inflammatory cytokine production in human immune cells, Inflammatory cytokines mediate response to injury or infection. However, if their levels are increased in the absence of an appropriate stimulus, chronic inflammation can occur. Chronic inflammation is associated with a number of pathologies including cancer. Stimulation of pro-inflammatory cytokine production by these toxicants is dependent on activation of ERK 1/2 and/or p38 MAPK pathways. MAPK pathways have the capacity to regulate translation by increasing phosphorylation of key translation regulatory proteins. There have been no previous studies examining the effects of TBT, DBT, or PCP on translation. The current study shows that ribosomal protein S6 (S6), eukaryotic initiation factor 4B (eIF4B), and eIF4E are phosphorylated (activated) and/or their total levels are elevated in response to each of these compounds at concentrations found in human blood. Activation/increased levels of translational proteins occurred at concentrations of the compounds that have been shown to elevate pro-inflammatory cytokine production, but where there is no increase in mRNA for those proteins was seen. Compound-stimulated increases in translation appear to be part of the mechanism by which they elevate protein production in immune cells. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is known as an endocrine-disrupting chemical. This study investigated the effects and possible mechanisms of TBT exposure on inducing human articular chondrocyte senescence in vitro at the human-relevant concentrations of 0.01–0.5 μM and mouse articular cartilage aging in vivo at the doses of 5 and 25 μg/kg/day, which were 5 times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively. TBT significantly increased the senescence-associated β-galactosidase activity and the protein expression levels of senescence markers p16, p53, and p21 in chondrocytes. TBT induced the protein phosphorylation of both p38 and JNK mitogen-activated protein kinases in which the JNK signaling was a main pathway to be involved in TBT-induced chondrocyte senescence. The phosphorylation of both ataxia-telangiectasia mutated (ATM) and histone protein H2AX (termed γH2AX) was also significantly increased in TBT-treated chondrocytes. ATM inhibitor significantly inhibited the protein expression levels of γH2AX, phosphorylated p38, phosphorylated JNK, p16, p53, and p21. TBT significantly stimulated the mRNA expression of senescence-associated secretory phenotype (SASP)-related factors, including IL-1β, TGF-β, TNF-α, ICAM-1, CCL2, and MMP13, and the protein expression of GATA4 and phosphorylated NF-κB-p65 in chondrocytes. Furthermore, TBT by oral gavage for 4 weeks in mice significantly enhanced the articular cartilage aging and abrasion. The protein expression of phosphorylated p38, phosphorylated JNK, GATA4, and phosphorylated NF-κB-p65, and the mRNA expression of SASP-related factors were enhanced in the mouse cartilages. These results suggest that TBT exposure can trigger human chondrocyte senescence in vitro and accelerating mouse articular cartilage aging in vivo. [ABSTRACT FROM AUTHOR]

Organotins such as tributyltin chloride (TBT), are highly diffused environmental pollutants, which act as metabolism disrupting chemicals, i.e. may interfere with fat tissue differentiation, as well as with neuroendocrine circuits, thus impairing the control of energetic balance. We have previously demonstrated that adult exposure to TBT altered the expression of neuropeptides in the hypothalamus. In this study, we orally administered daily a solution containing oil, or TBT (0.25, 2.5, or 25 μg/kg body weight/day) to pregnant females from gestational day 8 until birth, and to their pups from day 0 until post‐natal day 21. Our results showed that TBT exposure of female mice during gestation and of pups during lactation permanently altered the feeding efficiency of pups of both sexes and subcutaneous fat distribution in adult males. In addition, the neuropeptide Y system was affected at the level of the paraventricular nucleus, with a decrease in immunoreactivity in both sexes (significant in females for all TBT doses and in males only for intermediate TBT doses), while no effect was observed in other hypothalamic areas (arcuate, ventromedial and dorsomedial nuclei). Metabolic syndrome, as well as obesity and diabetes, which are significant health issues, are considered multifactorial diseases and may be caused by exposure to metabolic disruptors, both in adults and during perinatal life. In addition, our work indicates that TBT doses defined as the tolerably daily intake had a profound and sex‐specific long‐term effect. [ABSTRACT FROM AUTHOR]

An efficient radical cyclization of suitably functionalized ynamides to nitrogen-containing heterocycles is reported. Upon reaction with tributyltin hydride in the presence of catalytic amounts of AIBN in toluene at 80 °C, a range of ynamides bearing a N -iodopropyl chain could be smoothly cyclized, in a highly regio- and stereoselective manner, to the corresponding 2-arylidenepyrrolidines in good to excellent yields. The exocyclic double bond was in addition shown to be an excellent anchor for further chemical diversification and the generality of this radical cyclization could be highlighted by its extension to the synthesis of other nitrogen heterocycles including piperidines, azepanes, pyrazolidines and hexahydropyridazines. [ABSTRACT FROM AUTHOR]

Liza haematocheila is exposed to various chemical contaminants from anthropogenic sources, including tributyltin chloride (TBTC). Yet the toxicity mechanism of TBTC on haarder remains unclear. The haarder was exposed to different doses (0, 10%, 20%, and 50% of LC 50 -96 h) of TBTC. In this study, the results revealed its high bioaccumulation in the livers and significant alteration for development. The activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase decreased after 96-h exposure to TBTC, this accompanied by an increased malondialdehyde level. TBTC exposure caused the intense production of reactive oxygen species, a reduction in total blood cell count in serum, and apoptosis-related alterations in livers, indicating that enhanced oxidative stress occurred in the process of TBTC exposure. Histological results revealed angiorrhexis and infiltration of inflammatory cells, vacuolar degeneration of hepatocytes in the livers, and swelling, fusion, and disintegration of gill organs. Interestingly, the obtained transcriptional profiles indicated that high doses of TBTC caused energy disorder, apoptosis, and adipogenesis restriction mediated by cytokines and adipokines in Jak-STAT and adipocytokine signaling pathways. In summary, acute exposure to high doses of TBTC could impair the antioxidant system and pathways related to energy, apoptosis and adipogenesis, eventually posing a serious challenge to the fitness of haarder individuals and its fish populations as marine resources. [Display omitted] • Tributyltin chloride (TBTC) bioaccumulated highly in haarder livers. • Apoptosis was induced by TBTC in haarder livers. • TBTC caused transcriptome changes in haarder livers. • TBTC caused energy disorder and adipogenesis restriction in haarder. [ABSTRACT FROM AUTHOR]

Standard methods of microbial cultivation only enable the isolation of a fraction of the total environmental bacteria. Numerous techniques have been developed to increase the success of isolation and cultivation in the laboratory, some of which derive from diffusion chambers. In a diffusion chamber, environmental bacteria in agar medium are put back in the environment to grow as close to their natural conditions as possible, only separated from the environment by semi-permeable membranes. In this study, the iChip, a device that possesses hundreds of mini diffusion chambers, was used to isolate tributyltin (TBT) resistant and degrading bacteria. IChip was shown to be efficient at increasing the number of cultivable bacteria compared to standard methods. TBT-resistant strains belonging to Oceanisphaera sp., Pseudomonas sp., Bacillus sp. and Shewanella sp. were identified from Liverpool Dock sediment. Among the isolates in the present study, only members of Pseudomonas sp. were able to use TBT as a sole carbon source. It is the first time that members of the genus Oceanisphaera have been shown to be TBT-resistant. Although iChip has been used in the search for molecules of biomedical interest here we demonstrate its promising application in bioremediation. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is known as an endocrine-disrupting chemical abundant in the aquatic environment. In the present study, zebrafish fish embryos were used to observe the chronic toxicity of TBT. Fish embryo toxicity analysis was carried out for different TBT concentrations (100, 50, 25, 12.5, 6.2, and 3.1 ng/L) and fertilized eggs were used to test each concentration effect. Fertilized eggs in 24-well plates (20 eggs in each well) were incubated at 26°C for four days and embryo coagulation, heartbeat of the embryo and mortality lethal endpoints (LC50 values) were recorded after 8, 24, 48, and 96 h. The results revealed that 100% coagulations of the embryos occurred at TBT doses of 50 and 100 ng/L. The coagulation significantly increased in a dose-dependent manner and TBT might induce coagulation of zebrafish embryos. Heartbeat changes were significantly decreased (p<0.05) in a dose-dependent manner at different TBT doses. LC50 values of TBT for zebrafish embryos were 19.9, 11.7, 7.3, and 5.2 ng/L at 8, 24, 48, and 96 h, respectively. The percentage of mortality was higher in embryos for the trace level of TBT, indicating that embryos are more sensitive to TBT toxicity. Hence, TBT is highly toxic and leads to a lethal effect on the zebrafish embryo, resulting in species extinction and declining biodiversity in the aquatic environment. [ABSTRACT FROM AUTHOR]

The present investigation focused on the structure and demonstration of partial inhibition of spermatogenesis in male albino rats through pentacoordinate tributyltin (IV) complex of sterically blocked Schiff base of heterocyclic β‐diketone having the general formula Bu3SnL (where). The aid of physicochemical and spectral analysis suggested the plausible structure of this complex. The density functional theory (DFT) provides the optimized structure of the tributyltin (IV) complex. The computational study of the tributyltin (IV) complex evaluated the thermodynamic parameters, molecular orbitals, principal quantum chemical descriptors, and chemical reactivity. The experimental animals contain three groups, each consisting of nine animals. The male fertility of albino rats of groups II and III treated with tributyltin (IV) complex of sterically blocked Schiff base of heterocyclic β ‐diketone at 10 and 20 mg/kg body wt/day compared with group I during 90 days of the investigation was impaired consistently. Accordingly, the quality and quantity of sperms obtained from cauda epididymis deteriorated in both treatment groups compared with control animals. Blood testes barrier ruptured in the seminiferous tubules as a result of disordered germinal epithelium, substantial loss of germ cells, and remaining germ cell bursting, which stopped spermatogenesis at stage 13 of spermiogenesis. The findings of the study suggest that this complex partially inhibits spermatogenesis. Identifying some toxicophores scaffolds of the complex appears to be a significant contributor to the complete inhibition of spermatogenesis. [ABSTRACT FROM AUTHOR]

Context: Male exposure to environmental toxicants can disrupt spermatogenesis and sperm function. However, consequences of environmentally relevant organotin exposure to post-ejaculatory mammalian spermatozoa on fertility are poorly understood. Aims: Determine the consequences of tributyltin chloride (TBT) exposure on post-ejaculatory sperm function and subsequent embryo development. Methods: Frozen-thawed bovine sperm were exposed to TBT (0.1–100 nM) for 90 min (acute) and 6 h (short-term) followed by quantification of multiple sperm kinematics via computer aided sperm analysis. JC-1 dye was used to measure mitochondrial membrane potential. Sperm were then exposed to TBT for 90 min in non-capacitating conditions, washed several times by centrifugation and applied to gamete co-incubation for in vitro embryo production to the blastocyst stage. Key results: 100 nM TBT decreased total motility (88 vs 79%), progressive motility (80 vs 70%) curvilinear velocity and beat-cross frequency for 90 min with similar phenotypes at 6 h (P < 0.05). Sperm mitochondrial membrane potential was lower in 10 and 100 nM groups after 6 h (P ≤ 0.05). Embryos fertilised from TBT-exposed sperm had reduced cleavage rate (80 vs 62%) and 8–16 cell morula development (55 vs 24%) compared to development from unexposed sperm. Conclusions: Exposure of post-ejaculatory mammalian sperm to TBT alters sperm function through lowered motility and mitochondrial membrane potential. Fertilisation of oocytes with TBT-exposed sperm reduces embryo development through mechanisms of paternal origin. Implications: Acute and short-term environmental exposure of post-ejaculatory sperm to organotins and endocrine disrupting chemicals such as TBT contribute to idiopathic subfertility and early embryo loss. Environmental contaminant exposure to humans and animals is a global concern for negative effects on reproductive health and fertility. Consequences of the common and environmentally stable compound tributyltin chloride on post-ejaculatory sperm exposure were previously unknown and established herein to alter sperm function through reducing embryo development. These findings indicate that short-term exposure to environmental contaminants impact male fertility through a mechanism of paternal origin that negatively alters embryo development. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is extensively applied as an antifouling mediator, and it is well-known as an endocrine disrupting chemical. However, it remains elusive whether TBT can affect the development of pubertal Leydig cells (LCs), as a part of its endocrine mechanism of action. In this study, male Sprague Dawley rats (35-day-old) orally received TBT (0, 1, or 5 mg/kg) for 24 days. Immature LCs (ILCs) were separated from 35-day-old rats, and the cells were exposed to TBT at various concentrations (0, 0.05, 0.5, 1, or 5 μM) for 24 h. In vivo TBT treatment decreased the number of LCs and inhibited androgen production (2.92 ± 0.44, 1.16 ± 0.29, and 0.67 ± 0.10 ng/ml after treatment with TBT at 0, 1, and 5 mg/kg, respectively). In vitro TBT treatment reduced androgen production, cell viability, and cell cycle progression, while increased the levels of reactive oxygen species (ROS) along with subsequent apoptosis, particularly at the concentration of 5 μM. According to in vitro and in vivo findings, TBT downregulated the expression levels of genes that could control steroidogenesis (Hsd17b3, Scarb1 , Hsd3b1 , and Star), and decreased protein levels due to potential reduction of NR5A1 (Nr5a1). In summary, TBT inhibited cholesterol transport and activities of certain steroidogenic enzymes, thereby leading to the reduction of androgen production. • TBT decreases Leydig cell number and inhibits androgen production in vivo. • TBT lowers androgen production and reduces cell viability in vitro. • TBT induces reactive oxygen species and apoptosis in vitro. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) can be used as an antifouling agent with anticorrosive, antiseptic and antifungal properties and is widely used in wood preservation and ship painting. However, it has recently been found that TBT can be harmful to aquatic organisms. In this study, to gain insight into the effects of TBT with respect to the development of the cardiovascular system in zebrafish embryos, zebrafish embryos were exposed to different concentrations of TBT solutions (0.2 μg/L, 1 μg/L, and 2 μg/L) at 2 h post-fertilization (hpf) TBT exposure resulted in decreased hatchability and heart rate, deformed features such as pericardial edema, yolk sac edema, and spinal curvature in zebrafish embryos, and impaired heart development. Expression of cardiac development-related genes (vmhc , myh6 , nkx2.5 , tbx5a , gata4 , tbx2b , nppa) is dysregulated. Transgenic zebrafish Tg (fli1 : EGFP) were used to explore the effects of TBT exposure on vascular development. It was found that TBT exposure could lead to impaired development of intersegmental vessels (ISVs), common cardinal vein (CCV), subintestinal vessels (SIVs) and cerebrovascular. The expression of vascular endothelial growth factor (VEGF) signaling pathway-related genes (flt1 , flt4 , kdr , vegfa) was downregulated. Biochemical indices showed that ROS and MDA levels were significantly elevated and that SOD and CAT activities were significantly reduced. The expression of key genes for prostacyclin synthesis (pla2 , ptgs2a , ptgs2b , ptgis , ptgs1) is abnormal. Therefore, it is possible that oxidative stress induced by TBT exposure leads to the blockage of arachidonic acid (AA) production in zebrafish embryos, which affects prostacyclin synthesis and consequently the normal development of the heart and blood vessels in zebrafish embryos. [Display omitted] • Tributyltin induces developmental toxicity in zebrafish. • Tributyltin causes developmental defects in the cardiovascular system of zebrafish embryos. • Tributyltin exposure induced oxidative stress in zebrafish. • The cardiovascular toxicity caused by Tributyltin may be related to oxidative stress. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is one of the most harmful contaminants ever released into the aquatic environment. Despite being banned, it is still present at many locations throughout the world. Its degradation in sediment mainly occurs through microbial biodegradation, a process that remains unclear. This study therefore aimed at better understanding TBT biodegradation in estuarine sediment and the microbial community associated with it. Microcosm experiments were set up, embracing a range of environmental control parameters. Major community shifts were recorded, mainly attributed to the change in oxygen status. The highest percentage of degradation (36,8%) occurred at 4 °C in anaerobic conditions. These results are encouraging for the in-situ bioremediation of TBT contaminated muddy sediment in temperate ports worldwide. However, with TBT able to persist in the coastal environment for decades when undisturbed in anoxic sediment, further research is needed to fully understand the mechanisms that triggered this biodegradation observed in the microcosms. [Display omitted] • TBT biodegradation occurs in anoxic conditions in Liverpool docks sediment. • TBT biodegradation activity is held by psychrophilic anaerobic microorganisms. • Surprisingly, no TBT but DBT aerobic biodegradation was recorded at 15 °C. • In-situ bioremediation of TBT contaminated sediment is likely implementable. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is a biocide used in the formulation of antifouling paints and it is highly harmful. Despite the ban, the compound persists in the environment, contaminating marine foodstuffs and household products. Therefore, considering the route of exposure to the contaminant, the gastrointestinal tract (GIT) acts as an important barrier against harmful substances and is a potential biomarker for understanding the consequences of these agents. This work aimed to evaluate histological and neuronal alterations in the duodenum of male Wistar rats that received 20 ng/g TBT and 600 ng/g via gavage for 30 consecutive days. After the experimental period, the animals were euthanized, and the duodenum was intended for neuronal histochemistry (total and metabolically active populations) and histological routine (morphometry and histopathology). The results showed more severe changes in neuronal density and intestinal morphometry in rats exposed to 20 ng/g, such as total neuronal density decrease and reduction of intestinal layers. In rats exposed to 600 ng/g of TBT, it was possible to observe only an increase in intraepithelial lymphocytes. We conclude that TBT can be more harmful to intestinal homeostasis when consumed in lower concentrations. • The gastrointestinal tract and its components stand out as biomarkers. • TBT compromises the morphophysiology of the intestinal barrier and the enteric nervous system. • The gastrointestinal tract has high plastic potential and different compensatory responses. • The presence of TBT leads to intense inflammatory responses in the organ. [ABSTRACT FROM AUTHOR]

Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress. • TBTC caused cytotoxicity, DNA and chromosome damage effects. • TBTC significantly increased exosomal secretion. • Exosomal secretion alleviated the toxic effects caused by TBTC. • Exosomes transported TBTC out of the source cells. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT), an organotin endocrine-disrupting substance, is recognized as one of the important toxic environmental pollutants. The present study was carried out to investigate the toxic effects of TBT on behavior and the ovary of adult zebrafish with a focus on oxidative stress markers and oocyte maturation. Adult zebrafish were exposed to three different concentrations (125, 250, and 500 ng/L of water) of TBT for 28 days. TBT exposure produced a concentration-dependent negative effect on the body weight and behavior (anxiety-like symptoms) of adult zebrafish. Alterations in the activity of superoxide dismutase (SOD) and catalase (CAT), the total antioxidant capacity of ovarian tissue by the highest exposure level of TBT resulted in lipid peroxidation as indicated by increased malondialdehyde (MDA) level. The numbers of early-vitellogenic oocytes were significantly increased in zebrafish exposed to TBT as low as 125 ng/L. However, the numbers and size of fully-grown (mature) oocytes were significantly reduced in the highest exposure group only. Correlation between the MDA level and pre-vitellogenic oocytes in the 500 ng/L group indicated that lipid peroxidation prevented the maturation of pre-vitellogenic oocytes. TBT exposure produced significant histological changes in the ovary as evidenced by disturbed maturation of oocytes. In conclusion, TBT adversely affected the maturation of oocytes in zebrafish ovary through oxidative stress-mediated mechanisms. • Tributyltin (TBT) exposure negatively affected the body weight and behavior of adult zebrafish. • TBT exposure caused oxidative stress on the ovary. • TBT-exposed fish showed histological changes in the ovary. • TBT prevented the maturation of pre-vitellogenic oocytes and reduced the number and size of fully-grown oocytes. [ABSTRACT FROM AUTHOR]

Complement component 8gamma (C8γ), a member of the lipocalin protein family, is suggested to act as a carrier protein for various chemicals. Although C8γ has been identified in both humans and rodents for some time, our understanding of the species differences in its chemical binding properties remains limited. In the present study, with the aim to elucidate the potential role of C8γ as a carrier protein in both humans and mice, we conducted a radioligand binding assay to examine the chemical binding properties of human C8γ (hC8γ) and mouse C8γ (mC8γ). Scatchard analysis revealed that [14C]TPT bound to hC8γ with an equilibrium dissociation constant (K d) of 64.2 ± 32.4 nM, comparable to that of [14C]TPT to mC8γ. Competitive ligand-binding assays demonstrated binding of TPT and TBT to hC8γ, while diphenyltin, dibutyltin, monophenyltin, monobutyltin, and tetrabutyltin did not exhibit binding. These results suggest that for effective binding to C8γ, chemicals must possess substituents of appropriate bulkiness. Further analyses with other group 14 compounds with triphenyl substituents revealed that a central metal atom, rather than a central non-metal or semi-metal atom, is crucial for specific binding to both hC8γ and mC8γ. Overall our findings imply that C8γ may play a role in the physiological or toxicological actions of group 14 metal compounds with tributyl or triphenyl substituents by binding to these chemicals in both humans and mice. [Display omitted] • Complement component 8γ (C8γ) binds to trisubstituted organometallic compounds. • Substituents of suitable bulk are needed for chemicals to bind effectively to C8γ. • Human C8γ exhibits similar chemical binding properties to mouse C8γ. [ABSTRACT FROM AUTHOR]

The hypothalamic-pituitary-gonadal (HPG) axis is the principal modulator of reproductive function. Proper control of this system relies on several hormonal pathways, which make the female reproductive components susceptible to disruption by endocrine-disrupting chemicals such as tributyltin (TBT). Here, we review the relevant research on the associations between TBT exposure and dysfunction of the female HPG axis components. Specifically, TBT reduced hypothalamic gonadotropin-releasing hormone (GnRH) expression and gonadotropin release, and impaired ovarian folliculogenesis, steroidogenesis, and ovulation, at least in part, by causing abnormal sensitivity to steroid feedback mechanisms and deleterious ovarian effects. This review covers studies using environmentally relevant doses of TBT in vitro (1 ng—20 ng/ml) and in vivo (10 ng—20 mg/kg) in mammals. The review also includes discussion of important gaps in the literature and suggests new avenue of research to evaluate the possible mechanisms underlying TBT-induced toxicity in the HPG axis. Overall, the evidence indicates that TBT exposure is associated with toxicity to the components of the female reproductive axis. Further studies are needed to better elucidate the mechanisms through which TBT impairs the ability of the HPG axis to control reproduction. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is an environmental pollutant that remains in marine sediments and is toxic to mammals. For example, TBT elicits neurotoxic and immunosuppressive effects on rats. However, it is not entirely understood how TBT causes toxicity. Autophagy plays a pivotal role in protein quality control and eliminates aggregated proteins and damaged organelles. We previously reported that TBT dephosphorylates mammalian target of rapamycin (mTOR), which may be involved in enhancement of autophagosome synthesis, in primary cultures of cortical neurons. Autophagosomes can accumulate due to enhancement of autophagosome synthesis or inhibition of autophagic degradation, and we did not clarify whether TBT alters autophagic flux. Here, we investigated the mechanism by which TBT causes accumulation of autophagosomes in SH-SY5Y cells. TBT inhibited autophagy without affecting autophagosome–lysosome fusion before it caused cell death. TBT dramatically decreased the acidity of lysosomes without affecting lysosomal membrane integrity. TBT decreased the mature protein level of cathepsin B, and this may be related to the decrease in lysosomal acidity. These results suggest that TBT inhibits autophagic degradation by decreasing lysosomal acidity. Autophagy impairment may be involved in the mechanism underlying neuronal death and/or T-cell-dependent thymus atrophy induced by TBT. • Tributyltin inhibits autophagic degradation before it causes cell death. • Tributyltin reduces lysosomal acidity without affecting lysosomal membrane integrity. • Tributyltin decreases mature cathepsin B protein expression levels. [ABSTRACT FROM AUTHOR]

In the present work, new cross-linked networks based on furfural-functionalized poly(vinyl alcohol) (PVF) and maleimide compounds containing tributyltin groups were synthesized. The networks were obtained both as films and porous membranes. The structure of the compounds was confirmed by ATR-FTIR spectroscopy, and the morphology of the films/microporous membranes was investigated using scanning electron microscopy measurements (SEM), the differences between the films and membranes being evidenced. The mechanical performance and thermal stability of the membranes were examined by dynamic mechanical analysis (DMA) and thermogravimetry analysis (TGA), respectively. In addition, their water absorption and antimicrobial properties were thoroughly discussed. The antimicrobial activity of furfural-functionalized poly(vinyl alcohol) was significantly improved by its reaction with compounds containing tributyltin groups. [ABSTRACT FROM AUTHOR]

The investigation of sex bias and pseudohermaphroditism is a relatively unexplored area of research in the Neostromboidae. Here, we inform on these phenomena in a population of Gibberulus dekkersi Maxwell, Hernandez Duran, Rowell & Rymer, 2021 on Green Island, Great Barrier Reef. We collected 598 individuals, and noted the size of the cluster in which it occurred. Each individual was placed ventral side up and the body of the animal observed at the time of righting. Sex was determined by the presence or absence of a verge. During this sexing process, females were inspected for the presence of external male sexual organs to indicate the presence or absence of pseudohermaphroditism. We found that, overall, the population was not sexually biased towards one sex. However, we did find that individual clusters within the population showed significant sex bias, with different clusters favouring either males or females. Smaller clusters had a structural sex-ratio bias in favour of females. No evidence for pseudohermaphroditism was recorded, which indicates that the marine pollutant tributyltin (TBT) may not be present or at harmful levels in the surrounding environment. This study adds information from an unstudied Queensland taxon to the growing evidence on sex bias, clustering effects and pseudohermaphroditism within the Neostromboidae. [ABSTRACT FROM AUTHOR]

Sexual systems are surprisingly diverse, considering the ubiquity of sexual reproduction. Sequential hermaphroditism, the ability of an individual to change sex, has emerged multiple times independently across the animal kingdom. In molluscs, repeated shifts between ancestrally separate sexes and hermaphroditism are generally found at the level of family and above, suggesting recruitment of deeply conserved mechanisms. Despite this, molecular mechanisms of sexual development are poorly known. In molluscs with separate sexes, endocrine disrupting toxins bind the retinoid X receptor (RXR), activating ectopic male development in females, suggesting the retinoid pathway as a candidate controlling sexual transitions in sequential hermaphrodites. We therefore tested the role of retinoic acid signaling in sequentially hermaphroditic Crepidula snails, which develop first into males, then change sex, maturing into females. We show that retinoid agonists induce precocious penis growth in juveniles and superimposition of male development in females. Combining RXR antagonists with retinoid agonists significantly reduces penis length in induced juveniles, while similar treatments using retinoic acid receptor (RAR) antagonists increase penis length. Transcripts of both receptors are expressed in the induced penis. Our findings therefore show that retinoid signaling can initiate molluscan male genital development, and regulate penis length. Further, we show that retinoids induce ectopic male development in multiple Crepidula species. Species-specific influence of conspecific induction of sexual transitions correlates with responsiveness to retinoids. We propose that retinoid signaling plays a conserved role in molluscan male development, and that shifts in the timing of retinoid signaling may have been important for the origins of sequential hermaphroditism within molluscs. [Display omitted] • Retinoid agonists induce penis growth in sequentially hermaphroditic snails. • Blocking RXR or retinoic acid synthesis decreases penis length. • RXR , RAR , and CYP2 6 mRNA are expressed in the induced penis. • Shifts in retinoid timing may be involved in repeated evolution of hermaphroditism. [ABSTRACT FROM AUTHOR]

The pentafluorosulfanyl‐λ6‐perfluoroalkyl halides SF5CF2I, SF5CF2CF2Br, and SF5CF2CF2I were prepared for use in the syntheses of other SF5‐containing compounds. For example, new, convenient syntheses were developed for the hydro compounds SF5CF2H and SF5CF2CF2H from the reduction of these iodides or bromides with either triethylborane or tributyltin hydride. Herein, more thorough spectroscopic analyses of the hydro compounds are presented, including multinuclear NMR and vibrational spectroscopy, mass spectrometry, and computational chemistry. Unfortunately, under the conditions tried, little to no evidence was obtained for potential SF5(CF2)n‐ (where n=1 or 2) transfer reagents such as SF5(CF2)nSi(CH3)3 or Cu(CF2)nSF5. [ABSTRACT FROM AUTHOR]

[Display omitted] • TBT+HCD exposure impairs TYG index compared with CON, TBT and HCD treatment. • TBT+HCD exposure increases adipocyte hypertrophy compared with CON, TBT and HCD treatment. • TBT+HCD exposure reduces AMH levels compared with CON, TBT and HCD treatment. • TBT+HCD exposure increases FSH levels compared with CON, TBT and HCD treatment • TBT+HCD exposure worse POF features compared with CON, TBT and HCD treatment. Exposure to the obesogen tributyltin (TBT) alone or high carbohydrate diet (HCD) alone leads to obesity and reproductive complications, such as premature ovary failure (POF) features. However, little is known about interactions between TBT and nutrition and their combined impact on reproduction. In this study, we assessed whether acute TBT and HCD exposure results in reproductive and metabolic irregularities. Female rats were treated with TBT (100 ng/kg/day) and fed with HCD for 15 days and metabolic and reproductive outcomes were assessed. TBT and HCD rats displayed metabolic impairments, such as increased adiposity, abnormal lipid profile and triglyceride and glucose (TYG) index, worsening adipocyte hypertrophy in HCD-TBT rats. These metabolic consequences were linked with reproductive disorders. Specifically, HCD-TBT rats displayed irregular estrous cyclicity, high follicle-stimulating hormone (FSH) levels, low anti-Müllerian hormone (AMH) levels, reduction in ovarian reserve, and corpora lutea (CL) number, with increases in atretic follicles, suggesting that HCD-TBT exposure exacerbated POF features. Further, strong negative correlations were observed between adipocyte hypertrophy and ovarian reserve, CL number and AMH levels. HCD-TBT exposure resulted in reproductive tract inflammation and fibrosis. Collectively, these data suggest that TBT plus HCD exposure leads to metabolic and reproductive abnormalities, exacerbating POF features in female rats. [ABSTRACT FROM AUTHOR]

Background: Tributyltin, a well-known endocrine disruptor, is widely used in agriculture and industry. Previous studies have shown that tributyltin could cause deleterious effects on bone health by impairing the adipo-osteogenic balance in bone marrow.Methods: To investigate further the effects of tributyltin on bone, weaned male SD rats were treated with tributyltin (0.5, 5 or 50 μg·kg- 1) or corn oil by gavage once every 3 days for 60 days in this study. Then, we analyzed the effects of tributyltin on geometry, the polar moment of inertia, mineral content, relative abundances of mRNA from representative genes related to adipogenesis and osteogenesis, serum calcium ion and inorganic phosphate levels.Results: Micro-computed tomography analysis revealed that treatment with 50 μg·kg- 1 tributyltin caused an obvious decrease in femoral cortical cross sectional area, marrow area, periosteal circumference and derived polar moment of inertia in rats. However, other test results showed that exposure to tributyltin resulted in no significant changes in the expression of genes detected, femoral cancellous architecture, ash content, as well as serum calcium ion and inorganic phosphate levels.Conclusions: Exposure to a low dose of tributyltin from the prepubertal to adult stage produced adverse effects on skeletal architecture and strength. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) remains a global health concern. The primary route of human exposure to TBT is either through ingestion or skin absorption, but TBT's effects on the peripheral nervous system have still not been investigated. Therefore, we exposed in vitro sensory dorsal root ganglion (DRG) neurons to TBT at a concentration of 50–200 nM, which is similar to the observed concentrations of TBT in human blood samples. We observed that TBT causes extensive axon degeneration and neuronal death in the DRG neurons. Furthermore, we discovered that TBT causes an increase in both cytosolic and mitochondrial calcium levels, disrupts mitochondrial dynamics, decreases neuronal ATP levels, and leads to the activation of calpains. Additional experiments demonstrated that inhibition of calpain activation prevented TBT-induced fragmentation of neuronal cytoskeletal proteins and neuronal cell death. Thus, we conclude that calpain activation is the key executioner of TBT-induced peripheral neurodegeneration. [ABSTRACT FROM AUTHOR]

The declining rate of male fertility is a growing concern. Tributyltin (TBT) is a well-known endocrine disruptor (ED), that induces imposex in female gastropods and is widely used in various industrial applications. The aim of this study was to evaluate the toxic effects of TBT on the testes of adult albino rats and the possible role of omega-3. Forty two adult male albino rats were divided into five groups; control group (Group I) and four experimental groups: omega-3 treated group, TBT treated group, TBT & omega-3 treated group and follow up group. At the end of the study, the rats were subjected to biochemical, histological, immunohistochemical staining for Ki-67 and seminal examinations. Our results clarfied that TBT induced a significant decrease in testosterone, FSH, LH and serum glutathione peroxidase levels and a significant increase in the serum Malondialdehyde as compared to the control group. Tributyltin induced disorganization and shrinkage of seminiferous tubules, apoptosis, cellular damage and marked reduction in the germinal epithelium. A significant decrease in the cell proliferation and arrested spermatogenesis were also detected. Seminal analysis of TBT group showed a significant affection of all parameters as compared to other groups. Omega-3 ameliorated all of these hazardous effects. Follow up group still showed toxic effects. In conclusion, TBT has a toxic effect on the testis. Increased testicular oxidative stress, cellular damage and arrest of spermatogenesis with attenuation in antioxidant defenses are all contributing factors. Omega-3 can protect against TBT induced reproductive toxicity. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT), an organotin compound, is hazardous in aquatic ecosystems. However, the mechanisms underlying TBT-induced central nervous system (CNS) toxicity remain to be determined especially in freshwater aquatic vertebrates. The aim of present study was to investigate the effects of chronic exposure to TBT on brain functions in a freshwater teleost the adult wild-type zebrafish (Danio rerio). Fish were exposed to sublethal concentrations of TBT (10, 100 or 300 ng/L) for 6 weeks. The influence of long-term TBT exposure was assessed in the brain of zebrafish with antioxidant related indices including malondialdehyde (MDA) levels and total antioxidant capacity, neurological parameters such as activities of acetylcholinesterase, and monoamine oxidase as well as levels of nitric oxide, dopamine, 5-hydroxytryptamine. In addition indices related to sensitivity of toxic insult such as cytochrome P450 1 regulation and heat shock protein 70 were determined. The regulation of related genes involved in endoplasmic reticulum stress (ERS), apoptosis and Nrf2 pathway were measured. Adverse physiological and biochemical responses were significantly enhanced in a concentration-dependent manner reflecting neurotoxicity attributed to TBT exposure. Our findings provide further insight into TBT-induced toxicity in wild-type zebrafish. and enhance our understanding of the molecular mechanisms underlying TBT-initiated CNS effects. [ABSTRACT FROM AUTHOR]

The tropical estuarine guppy Poecilia vivipara was used to address fish early life stage toxicity caused by the antifouling contaminant tributyltin. Six‐day‐old P. vivipara were exposed for 7 d to control water and waterborne tributyltin at 15.8, 83.8, 716, and 818 ng tin (Sn) L–1. After exposure, swimming, feeding, growth, and eye histological endpoints were evaluated. Histopathological analysis of the retinal pigment epithelium (RPE) indicated alterations in pigment positioning at all tributyltin concentrations. A dose‐dependent increase in photoreceptor layer disorganization and iris melanin hyperpigmentation was verified, and high frequencies of RPE invaginations and iris epithelial cell atrophy were observed even at the lowest exposure concentration of 15.8 ng Sn L–1. At the highest exposure level (818 ng Sn L–1) fish also presented reductions in swimming speed, swimming resistance, daily capture of Artemia nauplii, and growth in weight of 85, 60, 33, and 56% relative to controls, respectively. This association between retinal histopathology and reduced swimming and foraging behavior can reduce recruitment to the adult population. Environ Toxicol Chem 2020;39:1953–1963. © 2020 SETAC [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) chloride is an endocrine disrupting chemical associated with reproductive complications. Studies have shown that TBT targets the reproductive tract, impairing ovarian folliculogenesis, and uterine morphophysiology. In this investigation, we assessed whether subchronic and low dose of TBT exposure results in abnormal ovarian follicular reserve and other irregularities in female mice. TBT was administered to female mice (500 ng/kg/day for 12 days via gavage), and reproductive tract morphophysiology was assessed. We further assessed reproductive tract inflammation and oxidative stress. Improper functioning of the reproductive tract in TBT mice was observed. Specifically, irregular estrous cyclicity and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. In addition, improper follicular development and a reduction in antral follicles, corpora lutea, and total healthy ovarian follicles together with an increase in cystic follicles were apparent. Evidence of uterine atrophy, reduction in endometrial gland number, and inflammation and oxidative stress were seen in TBT mice. Further, strong negative correlations were observed between testosterone levels and primordial, primary, and total healthy ovarian follicles. Thus, these data suggest that the subchronic and low dose of TBT exposure impaired ovarian follicular reserve, uterine gland number, and other reproductive features in female mice. [ABSTRACT FROM AUTHOR]

Oyster reefs are vital to estuarine health, but they experience multiple stressors and globally declining populations. This study examined effects of hypoxia and tributyltin (TBT) on adult Eastern oysters (Crassostrea virginica) exposed either in the laboratory or the field following a natural hypoxic event. In the laboratory, oysters were exposed to either hypoxia followed by a recovery period, or to hypoxia combined with TBT. mRNA expression of HIF1-α and Tβ-4 along with hemocyte counts, biomarkers of hypoxic stress and immune health, respectively, were measured. In field-deployed oysters, HIF1-α and Tβ-4 expression increased, while no effect on hemocytes was observed. In contrast, after 6 and 8 days of laboratory-based hypoxia exposure, both Tβ-4 expression and hemocyte counts declined. After 8 days of exposure to hypoxia + TBT, oysters substantially up-regulated HIF1-α and down-regulated Tβ-4, although hemocyte counts were unaffected. Results suggest that hypoxic exposure induces immunosuppression which could increase vulnerability to pathogens. [ABSTRACT FROM AUTHOR]

• TBT and TPT induce the transcription of 11β-HSD2 in JEG-3 cells. • Upregulation of 11β-HSD2 results in reduced cortisol-dependent activation of the GR. • RXRα is involved in the TBT and TPT induced effect on 11β-HSD2. • Fludioxonil and chlorotriphenylsilane activate RXRα and induce 11β-HSD2 expression. Exposure to the environmental pollutants organotins is of toxicological concern for the marine ecosystem and sensitive human populations, including pregnant women and their unborn children. Using a placenta cell model, we investigated whether organotins at nanomolar concentrations affect the expression and activity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 11β-HSD2 represents a placental barrier controlling access of maternal glucocorticoids to the fetus. The organotins tributyltin (TBT) and triphenyltin (TPT) induced 11β-HSD2 expression and activity in JEG-3 placenta cells, an effect confirmed at the mRNA level in primary human trophoblast cells. Inhibition/knock-down of retinoid X receptor alpha (RXRα) in JEG-3 cells reduced the effect of organotins on 11β-HSD2 activity, mRNA and protein levels, revealing involvement of RXRα. Experiments using RNA and protein synthesis inhibitors indicated that the effect of organotins on 11β-HSD2 expression was direct and caused by increased transcription. Induction of placental 11β-HSD2 activity by TBT, TPT and other endocrine disrupting chemicals acting as RXRα agonists may affect placental barrier function by altering the expression of glucocorticoid-dependent genes and resulting in decreased availability of active glucocorticoids for the fetus, disturbing development and increasing the risk for metabolic and cardiovascular complications in later life. [ABSTRACT FROM AUTHOR]

Lactate dehydrogenase (LDH) in spermatozoa of three fish species was studied to determine its role in sperm cell bioenergetics in normal and polluted conditions. The adenylate energy charge (AEC) has been used as the measure of energy storage for adenine nucleotide pool of living cells and tributyltin (TBT) as a model toxicant. It was demonstrated that carp Cyprinus carpio Linnaeus, 1758 spermatozoa exhibit higher LDH activity than catfish Clarias gariepinus (Burchell, 1822) and herring Clupea harengus Linnaeus, 1758 spermatozoa. Native electrophoretic pattern of LDH from spermatozoa compared to somatic tissues extract shows nine LDH isoenzymes in carp spermatozoa, two LDH isoenzymes in herring and one LDH isoenzyme in catfish spermatozoa. It was confirmed that lactate plus pyruvate, which are the substrates for LDH seems to maintain AEC value. It indicates ATP synthesis in tricarboxylic acid cycle prevails upon the ATP utilization in catfish spermatozoa. It was noticed that LDH-B4 is more strongly inhibited by TBT in herring than the nine LDH isoenzymes in carp spermatozoa which confirms that herring spermatozoa may be more sensitive for pollution by decreasing their energetic state. LDH role in maintaining physiological bioenergetic state of spermatozoa is also discussed. [ABSTRACT FROM AUTHOR]

A subset of environmental chemicals acts as "obesogens" as they increase adipose mass and lipid content in livers of treated rodents. One of the most studied class of obesogens are the tin-containing chemicals that have as a central moiety tributyltin (TBT), which bind and activate two nuclear hormone receptors, Peroxisome Proliferator Activated Receptor Gamma (PPARG) and Retinoid X Receptor Alpha (RXRA), at nanomolar concentrations. Here, we have tested whether TBT chloride at such concentrations may affect the neutral lipid level in two cell line models of human liver. Indeed, using high content image analysis (HCA), TBT significantly increased neutral lipid content in a time- and concentration-dependent manner. Consistent with the observed increased lipid accumulation, RNA fluorescence in situ hybridization (RNA FISH) and RT-qPCR experiments revealed that TBT enhanced the steady-state mRNA levels of two key genes for de novo lipogenesis, the transcription factor SREBF1 and its downstream enzymatic target, FASN. Importantly, pre-treatment of cells with 2-deoxy-D-glucose reduced TBT-mediated lipid accumulation, thereby suggesting a role for active glycolysis during the process of lipid accumulation. As other RXRA binding ligands can promote RXRA protein turnover via the 26S proteasome, TBT was tested for such an effect in the two liver cell lines. We found that TBT, in a time- and dose-dependent manner, significantly reduced steady-state RXRA levels in a proteasome-dependent manner. While TBT promotes both RXRA protein turnover and lipid accumulation, we found no correlation between these two events at the single cell level, thereby suggesting an additional mechanism may be involved in TBT promotion of lipid accumulation, such as glycolysis. [ABSTRACT FROM AUTHOR]

The development of polycystic ovary syndrome (PCOS) could be caused by exposure to environmental endocrine disrupting chemicals (EDCs). In the current study, two commonly found EDCs, bisphenol A (BPA) and tributyltin (TBT), were investigated for their effects on PCOS occurrence in neonatal female rats. TBT (10 and 100 ng kg−1 d−1), BPA (50 μg kg−1 d−1), and a mixture of the two (TBT 100 ng kg−1 d−1 with BPA 50 μg kg−1 d−1) were administered to female rats from postnatal day 1–16. TBT, BPA, and TBT + BPA treatment resulted in an irregular estrus cycle and disturbed ovarian development, with less corpora lutea and antral follicles, but more atretic follicles and cysts. In addition, serum testosterone and luteinizing hormone levels were significantly elevated, whereas a reduced level of serum sex hormone-binding globulin was observed after TBT100, BPA50, and TBT + BPA treatments. Moreover, gene expression analyses identified significant differential expression of the genes involved in a variety of biological pathways, such as lipid transport and steroidogenesis. Moreover, the expression level of proteins regulating lipid and androgen biosynthesis was elevated after the treatments. In conclusion, this study demonstrated that exposure to TBT, BPA, and a mixture of the two in newborn rats could contribute to a PCOS-like syndrome. The mechanism of PCOS pathogenesis caused by exposure to TBT and BPA is likely to be mediated by the lipid metabolism and steroidogenesis pathways. Our results provide novel insight into female reproduction affected by EDCs, which may be helpful for revealing the pathogenesis of PCOS. Image 1 • Neonatal exposure to TBT or BPA causes PCOS in adulthood of rats. • TBT or BPA induces PCOS possibly through altering steroidogenesis pathways. • Co-exposure with TBT and BPA does not show any antagonistic or additive effect. [ABSTRACT FROM AUTHOR]

Exposure to tin in the general US population is near ubiquitous, as determined using urinary tin levels measured by inductively coupled plasma mass spectrometry (ICP-MS). Urinary tin levels are associated with chronic health outcomes, such as diabetes; however, it is unclear if these associations are due to the presence of inorganic and organic forms of tin in urine. To address this knowledge gap, levels of total tin and several organotin compounds (OTCs) were measured in convenience urine samples from pregnant women and adults from Iowa, United States. Total tin and OTC levels in urine samples were quantified using ICP-MS and gas chromatography with pulsed flame photometric detection (GC-PFPD), respectively. ICP-MS detected tin in almost all urine samples from both study populations. Low levels of dibutyltin were detected in two out of fifty human urine samples. Importantly, storage of urine samples in plastic containers, but not HNO3-pretreated glass vials drastically reduced the recoveries of OTCs, in particular, tributyltin. Although their detection frequency is low, exposures to OTC should be considered when studying associations between human exposures to tin compounds and adverse health outcomes; however, urinary OTC levels measured in banked urine samples may not be suitable as biomarkers of OTC exposure. [ABSTRACT FROM AUTHOR]