Tributyltin perturbs femoral cortical architecture and polar moment of inertia in rat.

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.

Tributyltin reduces bone mineral density by reprograming bone marrow mesenchymal stem cells in rat.

Tributyltin (TBT), a proven endocrine disrupter, was widely used in industry and agriculture. Previous research showed that TBT could alter the balance between osteogenesis and adipogenesis, which may have significant consequences for bone health. Herein, we exposed male rats to TBT chloride (TBTCl) to evaluate the deleterious effects of TBT on bone. Exposure to 50 µg kg-1 TBT resulted in a significant decrease in bone mineral density (BMD) at the femur diaphysis region in the rat. A dose-dependent increase in lipid accumulation and adipocyte number was observed in the bone marrow (BM) of the femur. Meanwhile, TBTCl treatment significantly enhanced the expression of PPARγ and attenuated the expression of Runx2 and ß-catenin in BM. In addition, serum ALP activity of TBT-exposed rats also showed a dose-dependent decrease. These results suggest that TBT could reduce BMD via inhibition of the Wnt/ß-catenin pathway and skew the adipo-osteogenic balance in the BM of rats.

Tributyltin exposure induces gut microbiome dysbiosis with increased body weight gain and dyslipidemia in mice.

Gut microbiome dysbiosis plays a profound role in the pathogenesis of obesity and tributyltin (TBT) has been found as an environmental obesogen. However, whether TBT could disturb gut microbiome and the relationship between obesity induced by TBT exposure and alteration in gut microbiota are still unknown. In order to assess the association between them, mice were exposed to TBTCl (50 µg kg-1) once every three days from postnatal days (PNDs) 24 to 54. The results demonstrated that TBT exposure resulted in increased body weight gain, lager visceral fat accumulation and dyslipidemia in male mice on PND 84. Correspondingly, 16S rRNA gene sequencing revealed that TBT treatment decreased gut microbial species and perturbed the microbiome composition in mice. Furthermore, Pearson's corelation coefficient analysis showed a significantly negative correlation between the body weight and the alpha diversity of gut microbiome. These results suggested that TBT exposure could induce gut microbiome dysbiosis in mice, which might contribute to the obesity pathogenesis.

Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice.

Tributyltin (TBT), a proven environmental obesogen, functions as a nanomolar agonist of the peroxisome proliferator activated receptor-γ (PPARγ). However, the adverse effects of TBT on metabolism are incompletely understood. In this study, male ICR mice were administered TBT (5 and 50 µg·kg-1 ) by an intraperitoneal injection once every 3 days for 30 days from 28 days of age and bred for another 30 days after the last administration of TBT. We analyzed the effects of these exposures on the fat depot weights, serum lipid profile, serum leptin and adiponectin, hepatic lipid accumulation, and activity of AKT in the liver and skeletal muscle isolated from mice 8 mins after receiving an insulin injection. Pubertal exposure to TBTCl resulted in a higher body weight, increased epididymal and liver fat accumulation, hyperlipidemia, an elevated low-density lipoprotein/high-density lipoprotein ratio, serum adiponectin deficiency, worse glucose tolerance, and lower insulin-dependent AKT phosphorylation in the liver and muscle in mice. These results showed that TBT exposure induced peripheral insulin resistance and metabolic syndrome in mice.

Acrylamide Retards the Slow Axonal Transport of Neurofilaments in Rat Cultured Dorsal Root Ganglia Neurons and the Corresponding Mechanisms.

Chronic acrylamide (ACR) exposure induces peripheral-central axonopathy in occupational workers and laboratory animals, but the underlying mechanisms remain unclear. In this study, we first investigated the effects of ACR on slow axonal transport of neurofilaments in cultured rat dorsal root ganglia (DRG) neurons through live-cell imaging approach. Then for the underlying mechanisms exploration, the protein level of neurofilament subunits, motor proteins kinesin and dynein, and dynamitin subunit of dynactin in DRG neurons were assessed by western blotting and the concentrations of ATP was detected using ATP Assay Kit. The results showed that ACR treatment results in a dose-dependent decrease of slow axonal transport of neurofilaments. Furthermore, ACR intoxication significantly increases the protein levels of the three neurofilament subunits (NF-L, NF-M, NF-H), kinesin, dynein, and dynamitin subunit of dynactin in DRG neurons. In addition, ATP level decreased significantly in ACR-treated DRG neurons. Our findings indicate that ACR exposure retards slow axonal transport of NF-M, and suggest that the increase of neurofilament cargoes, motor proteins, dynamitin of dynactin, and the inadequate ATP supply contribute to the ACR-induced retardation of slow axonal transport.

Perinatal exposure to low doses of tributyltin chloride reduces sperm count and quality in mice.

Exposure to endocrine disruptors (EDs) during early development might lead to adverse health outcomes later in life. Tributyltin (TBT), a proven ED, is widely used in consumer goods and industrial products. Herein we demonstrate the effects of low doses of tributyltin chloride (TBTCl) on reproduction of male KM mice. Pregnant mice were administered by gavage with 0, 1, 10, or 100 µg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. TBTCl dramatically decreased sperm counts and motility on postnatal days (PNDs) 49 and 152. Meanwhile, a significant increase in sperm abnormality was observed in exposed mice on PND 49, but comparable to that in the control on PND 152. The histopathological analysis of testes of treated animals showed a dose-dependent increase in sloughing of germ cells in seminiferous tubules. Mice treated with 10 µg TBTCl/kg exhibited decreased intratesticular 17ß-estradiol (E2) levels on PND 49, and then followed by an obvious recovery on PND 152. While, no significant differences in serum E2, testosterone (T) levels and intratesticular T levels were detectable between control and TBTCl-exposed offspring at the sacrifice. These results suggest that perinatal TBTCl exposure is implicated in causing long lasting alterations in male reproductive system and these changes may persist far into adulthood.

Influence of planting patterns on fluoroquinolone residues in the soil of an intensive vegetable cultivation area in northern China.

Recent studies have demonstrated the persistence of antibiotics in soil, especially in areas of vegetable cultivation. However, there are very few studies of the influence of planting regimes on the levels of antibiotic pollution. This work introduces geographical-detector models to investigate the relationship between planting patterns (vegetable planting model, manure type and quantity, planting age, greenhouse area, and topographic elevation) and residual fluoroquinolones (FQs) in soil in a pilot project in Shouguang County, Shandong Province (the largest vegetable-producing area in China). The results led to the following findings. 1. The vegetable planting model is the major determinant of the spatial stratification of FQ in the soil. For example, the "cucumber-cucumber" model (growing cucumbers after cucumbers) has a three-fold power of determinant compared to the "pepper-melon" model (growing melons after peppers). 2. Planting age (years with continuous vegetable cultivation) does not necessarily affect the spatial distribution of FQ owing to their relatively short degradation period. 3. Interactions between risk factors were more significant than the individual factors for FQ pollution. In particular, the interaction between the vegetable planting model and amount of manure resulted in the highest pollution level. The findings of the present study make it possible to introduce effective and practical measures to alleviate pollution of soils by FQ in the study area. Adjustment of the vegetable cultivation models and application of chicken manure (less than 6 kg/m(2) manure annually with a more dry than fresh manure) could be an effective and flexible approach to alleviate FQ pollution.

Effects of perinatal exposure to low doses of tributyltin chloride on pregnancy outcome and postnatal development in mouse offspring.

Tributyltin (TBT), an endocrine-disrupting chemical, is well known to induce imposex in female gastropods. In this study, we assessed the effects of low doses of tributyltin chloride (TBTCl) on dams and their offspring. Pregnant mice were administered by gavage with 0, 1, 10, or 100 µg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. There were no TBT treatment-related deaths or clinical signs of toxicity for dams, and no treatment-related effects on body weight, litter sizes, gestational length of dams, and sex ratio, lactational body weight, postnatal survival, age at eruption of incisors, and eye opening of pups. However, at 100 µg/kg, TBTCl retarded the testes descent of male offspring. Behavioral tests showed a significant delay in cliff-drop aversion response in offspring of 10 and 100 µg/kg groups, but no significant difference in the righting reflex between control and TBT-exposed offspring was detectable. These results indicate that neurobehavioral toxicity seems to be one sensitive indicator to assess the risk of low doses of TBT.

Perinatal exposure to low doses of tributyltin chloride advances puberty and affects patterns of estrous cyclicity in female mice.

Tributyltin (TBT), a proven endocrine-disrupting chemical, is well known to induce imposex in female gastropods. Herein we demonstrate the effects of low doses of tributyltin chloride (TBTCl) on the female offspring of KM mice. Pregnant mice were administered by gavage with 0, 1, 10, or 100 µg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. TBTCl dramatically advanced the age of onset of vaginal opening (VO) and first vaginal estrus, and reduced body weights at VO and first estrus. Furthermore, perinatal treatment with TBTCl significantly reduced the number of days between VO and first estrus. In addition, female offspring from dams exposed to 10 and 100 µg kg(-1) TBTCl exhibited altered patterns of estrous cyclicity in adulthood. In conclusion, perinatal exposure to low doses TBTCl result in early puberty and impaired estrous cyclicity in female mice, which suggest that TBTCl might act as an estrogen agonist or/and a disruptor on hypothalamic-pituitary function in the present study.

Peripubertal exposure to low doses of tributyltin chloride affects the homeostasis of serum T, E2, LH, and body weight of male mice.

Previous studies have shown that tributyltin could act as an endocrine disruptor in mammals. However, the data on the low-dose effect of tributyltin in animals are still lacking. The objective of this study was to demonstrate the endocrine disruption induced by low levels of tributyltin chloride (TBTCl) in male KM mice. The animals were treated with 0.05 or 0.5 mg TBTCl/kg body weight/3 days from postnatal days (PNDs) 24 to 45, and killed on PNDs 49 and 84, respectively. Mice treated with 0.5 mg TBTCl/kg exhibited decreased serum and intratesticular testosterone (T) levels on PND 49 and then followed by an obvious recovery on PND 84. Furthermore, mice treated with 0.05 mg TBTCl/kg showed reduced serum 17ß-estradiol (E2) levels on PND 49. However, treatments with TBTCl resulted in a dose-dependent increase in serum E2 concentration of the mice on PND 84. Administration of TBTCl also decreased levels of serum luteinizing hormone and intratesticular E2 on PND 84. In addition, mice exposed to 0.05 mg/kg TBTCl exhibited an increase in body weight in the late stage of the experiment. These results indicate that treatment with low doses of TBTCl could disturb hormone homeostasis and body weight gain in rodents, and exposure to different levels of TBTCl might have different effects on changing some physiologic parameters.

Codoping Na+ to modulate the spectroscopy and photoluminescence properties of Yb3+ in CaF2 laser crystal.

Three kinds of Yb3+ - and Na+-codoped CaF2 laser crystal with different Na:Yb ratios of 0, 1.5, and 10 are grown by the temperature gradient technique. Room-temperature absorption, photoluminescence spectra, and fluorescence lifetimes belonging to the transitions between ground state 2F7/2 and excited state 2F5/2 of Yb3+ ions in the three crystals are measured to study the effect of Na+. Experimental results show that codoping Na+ ions in different Na:Yb ratios can modulate the spectroscopy and photoluminescence properties of Yb3+ ions in a CaF2 lattice in a large scope.