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Effect of bisphenol S on testicular tissue after low-dose nursing exposure
2022
Fenclová, Tereza | Chemek, Marouane | Havránková, Jiřina | Kolinko, Yaroslav | Sudová, Vendula | Moravec, Jiří | Navrátilová, Jana | Klein, Pavel | Králíčková, Milena | Nevoral, Jan
Exposure to endocrine disruptors such as bisphenols, can lead to and be the explanation for idiopathic infertility. In our study, we assessed the effect of exposure to bisphenol S (BPS) via breast milk on the testicular tissue health of adult male mice. Milking dams were exposed to BPS through drinking water (0.216 ng g bw/day and 21.6 ng g bw/day) from post-natal day 0–15. Although there was no significant difference in testicular histopathology between the control and experimental groups, we observed an increase in the number of tight and gap junctions in the blood-testis barrier (BTB) of adult mice after nursing BPS exposure. Moreover, there was an increase in oxidative stress markers in adult testicular tissue of mice exposed during nursing. Our nursing model indicates that breast milk is a route of exposure to an endocrine disruptor that can be responsible for idiopathic male infertility through the damage of the BTB and weakening of oxidative stress resistance in adulthood.
اظهر المزيد [+] اقل [-]Pyriproxyfen induces intracellular calcium overload and alters antioxidant defenses in Danio rerio testis that may influence ongoing spermatogenesis
2021
Staldoni de Oliveira, Vanessa | Gomes Castro, Allisson Jhonatan | Marins, Katiuska | Bittencourt Mendes, Ana Karla | Araújo Leite, Gabriel Adan | Zamoner, Ariane | Van Der Kraak, Glen | Mena Barreto Silva, Fátima Regina
We investigated the in vitro effects of pyriproxyfen on ionic balance in the testis of the zebrafish by measuring ⁴⁵Ca²⁺ influx. In vivo pyriproxyfen treatment was carried out to study oxidative stress, and conduct morphological analysis of the testis and liver. Whole testes were incubated in vitro with/without pyriproxyfen (10⁻¹², 10⁻⁹ or 10⁻⁶ M; 30 min) and ⁴⁵Ca²⁺ influx determined. To study pyriproxyfen’s mechanism of action, inhibitors/activators of ionic channels or pumps/exchangers, protein kinase inhibitors or a calcium chelator were added 15 min before the addition of ⁴⁵Ca²⁺ and pyriproxyfen. We evaluated the in vivo effects of 7 day exposure to waterborne pyriproxyfen (10⁻⁹ M) on reactive oxygen species (ROS) formation, lipid peroxidation, and reduced glutathione content (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and γ-glutamyltransferase (GGT) activity. Morphological analyses of the testis and liver were carried out after in vivo exposure of D. rerio to pyriproxyfen. Pyriproxyfen increased ⁴⁵Ca²⁺ influx by opening the voltage-dependent T-type channels (T-type VDCC), inhibiting sarco/endoplasmic reticulum ⁴⁵Ca²⁺-ATPase (SERCA) and the NCX exchanger (forward mode) and by mobilizing calcium from stores. The involvement of potassium channels and protein kinase C (PKC) was also demonstrated in pyriproxyfen-induced intracellular calcium elevation. In vivo pyriproxyfen treatment of D. rerio increased lipid peroxidation, decreased GSH content and increased GST activity in testes, in addition to increasing the number and size of spermatogonia cysts and inducing hepatocyte basophilia and dilation of blood vessels in the liver. The toxicity of pyriproxyfen is mediated by calcium overload, increased lipid peroxidation, and a diminished antioxidant capacity in the testis, due to GSH depletion, and altered spermatogenesis. The development of high basophilia in the liver suggests that pyriproxyfen may have estrogenic activity, possibly acting as an endocrine-disruptor. These findings indicate that these alterations may contribute to pyriproxyfen toxicity and spermatogenesis disruption.
اظهر المزيد [+] اقل [-]Effects of L-Glufosinate-ammonium and temperature on reproduction controlled by neuroendocrine system in lizard (Eremias argus)
2020
Zhang, Luyao | Chen, Li | Meng, Zhiyuan | Jia, Ming | Li, Ruisheng | Yan, Sen | Tian, Sinuo | Zhou, Zhiqiang | Diao, Jinling
In the context of global warming, an important issue is that many pesticides become more toxic, putting non-target organisms at higher risk of pesticide exposure. Eremias argus (a native Chinese lizard) was selected as animal model in this study. As a kind of poikilothermic vertebrate, E.argus is sensitive to temperature change. The experimental design [(with or without L-Glufosinate-ammonium (L-GLA) pollution × two temperatures (25 and 30 °C)] was used in this study for 90 days to identify the chronic effects of the pesticide–temperature interaction on the lizards’ neuroendocrine-regulated reproduction. Survival rate, body weight, clutch characteristics, testicular histopathology, the content of neurotransmitters and related enzyme activity, the level of sex steroid, the expression of Heat shock protein 70 (HSP70), antioxidant system, the accumulation and degradation of L-GLA were examined. Results showed that L-GLA disrupt reproduction of lizards through hypothalamus-pituitary-gonad (HPG) axis. In addition, temperature can not only change the environmental behavior of pesticides, but also alter the physiological characteristics of lizards. Thus, our results emphasized that temperature is an essential abiotic factor that should not be overlooked in ecotoxicological studies.
اظهر المزيد [+] اقل [-]Tissue-specific bioaccumulation, metabolism and excretion of tris (2-ethylhexyl) phosphate (TEHP) in rare minnow (Gobiocyprisrarus)
2020
Hou, Rui | Xu, Yiping | Rao, Kaifeng | Feng, Chenglian | Wang, Zijian
Tris (2-ethylhexyl) phosphate (TEHP) is one of the most commonly used organophosphorus flame retardant (OPFR) analogues and is commonly detected in surface water and sediments. Limited information is available about the metabolic pathway or metabolite formation related to TEHP in fish. In this study, rare minnows (Gobiocyprisrarus) were exposed to TEHP in static water for 30 d to investigate the bioaccumulation and metabolite distribution in the fish muscle, liver, kidney, gill, GI-tract, ovary and testis. Based on the estimated kᵤₚ,ₚₐᵣₑₙₜ and kd,ₚₐᵣₑₙₜ values, the bioconcentration factors (BCFₚₐᵣₑₙₜ) of TEHP in fish tissues were calculated in the order of kidney > ovary ≈ liver ≈ testis > gill ≈ GI-tract > muscle; this finding was consistent with the results of our previous study on other alkyl-substituted OPFRs. In addition, this study identified the metabolic profiles of TEHP in the liver. TEHP was oxidatively metabolized by the fish to a dealkylated metabolite (di 2-ethylhexyl phosphate; DEHP) and hydroxylated TEHP (OH-TEHP). OH-TEHP further underwent extensive phase II metabolism to yield glucuronic acid conjugates. DEHP was mainly distributed in rare minnow in the following order: liver > GI-tract > kidney ≫ other tissues. However, the metabolite showed lower accumulation potential in fish tissues than TEHP, with metabolite parent concentration factors (MPCFs) for DEHP of less than 0.1 in all the investigated tissues. The BCFₚₐᵣₑₙₜ values of TEHP in various fish tissues were only 9.0 × 10⁻³-7.2 × 10⁻⁴ times its estimated tissue-water partition coefficient (Kₜᵢₛₛᵤₑ₋wₐₜₑᵣ) values based on tissue lipid, protein and water contents, which indicated the significance of biotransformation in reducing the bioaccumulation potential of TEHP in fish. The toxicokinetic data in the present study help in understanding the tissue-specific bioaccumulation and metabolism pathways of TEHP in fish and highlight the importance of toxicology research on TEHP metabolites in aquatic organisms.
اظهر المزيد [+] اقل [-]Glyphosate-based herbicides influence antioxidants, reproductive hormones and gut microbiome but not reproduction: A long-term experiment in an avian model
2020
Ruuskanen, Suvi | Rainio, Miia J. | Gómez-Gallego, Carlos | Selenius, Otto | Salminen, Seppo | Collado, Maria Carmen | Saikkonen, Kari | Saloniemi, Irma | Helander, Marjo
Controversial glyphosate-based herbicides (GBHs) are the most frequently used herbicides globally. GBH residues in the wild, in animal and human food may expose non-target organisms to health risks, yet the developmental and cumulative effects of GBHs on physiology and reproduction remain poorly understood. We present the first long-term study on the effects of subtoxic GBH exposure (160 mg/kg) on multiple key physiological biomarkers (cellular oxidative status and neurotransmitters), gut microbiome, reproductive hormones, and reproduction in an avian model. We experimentally exposed in Japanese quail females and males (Coturnix japonica) to GBHs and respective controls from the age of 10 days–52 weeks. GBH exposure decreased hepatic activity of an intracellular antioxidant enzyme (catalase), independent of sex, but did not influence other intracellular oxidative stress biomarkers or neurotransmitter enzyme (acetylcholinesterase). GBH exposure altered overall gut microbiome composition, especially at a younger age and in females, and suppressed potentially beneficial microbes at an early age. Many of the microbial groups increased in frequency from 12 to 28 weeks under GBH exposure. GBH exposure decreased male testosterone levels both at sexual maturity and at 52 weeks of exposure, but did not clearly influence reproduction in either sex (maturation, testis size or egg production). Future studies are needed to characterize the effects on reproductive physiology in more detail. Our results suggest that cumulative GBH exposure may influence health and reproduction-related traits, which is important in predicting their effects on wild populations and global poultry industry.
اظهر المزيد [+] اقل [-]Selenium sources differ in their potential to alleviate the cadmium-induced testicular dysfunction
2020
Zhang, Cong | Huang, Yan | Talukder, Milton | Ge, Jing | Lv, Mei-Wei | Bi, Shao-Shuai | Li, Jin-Long
Cadmium (Cd), a major environmental contaminant, is closely associated with male reproductive health. Selenium (Se) has been recognized as an effective chemo-protectant against Cd toxicity, but the underlying mechanisms remain unclear. The objective of present study was to illustrate the toxic effect of Cd on testis, and then compare the antagonistic effect among different Se sources on growth performance, testicular damage, ion homeostasis, antioxidative potential, and the expression of selenotranscriptome and biosynthetic related factors in Cd-treated chicken. Male chickens were fed with (Ⅰ) Control group: basal diet; (Ⅱ) Cd group: basal diet with 140 mg/kg CdCl₂; (Ⅲ) YSe + Cd group: basal diet with 140 mg/kg CdCl₂ and 3 mg/kg Yeast-Se; (Ⅳ) NSe + Cd group: basal diet with 140 mg/kg CdCl₂ and 1 mg/kg Nano-Se; (Ⅴ) SSe + Cd group: basal diet with 140 mg/kg CdCl₂ and 3 mg/kg Na₂SeO₃. It was observed that different Se treatments dramatically alleviated Cd-induced testicular developmental disorder, ion homeostasis disorder, hormone secretion disorder and oxidative stress. Simultaneously, Se mitigated Cd-induced testicular toxicity by regulating selenoprotein biosynthetic related factors to promote selenoprotein transcription. Finally, this study indicated that dietary supplementation of Yeast-Se produced an acceptable Se form to protect testis from Cd exposure.
اظهر المزيد [+] اقل [-]Three organophosphate flame retardants (OPFRs) reduce sperm quality in Chinese rare minnows (Gobiocypris rarus)
2020
Chen, Rui | Hong, Xiangsheng | Yan, Saihong | Zha, Jinmiao
Organophosphate flame retardants (OPFRs) are widespread in the aquatic environment, but the effects of these chemicals on reproductive toxicity are far from clear. In this study, sperm quality in adult male Chinese rare minnows after exposure to tris-(2-butoxyethyl) phosphate (TBOEP), tris-(1,3-dichloro-2-propyl) phosphate (TDCIPP), and triphenyl phosphate (TPHP) was investigated. No obvious change in sperm concentration and vitality was observed after treatments, whereas significant changes in sperm velocity and morphology were found following all treatments (P < 0.05). Moreover, OPFR exposure significantly increased the apoptosis ratios in testis cells. Analysis of the transcriptomic data revealed that Na⁺/K⁺ ATPase (NKA) related genes were significantly downregulated, and the NKA enzyme activities after all treatments were significantly inhibited (P < 0.05). However, no obvious change in hormone levels in the groups exposed to TBOEP and TDCIPP was observed. These findings indicate that the OPFR-induced reduction of sperm quality might be due to the effects of OPFRs on NKA enzyme instead of changes in hormone levels.
اظهر المزيد [+] اقل [-]Differences in reproductive toxicity of TBBPA and TCBPA exposure in male Rana nigromaculata
2018
Zhang, Hangjun | Liu, Wenli | Chen, Bin | He, Jianbo | Chen, Feifei | Shan, Xiaodong | Du, Qiongxia | Li, Ning | Jia, Xiuying | Tang, Juan
Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are persistent toxic environmental pollutants that cause severe reproductive toxicity in animals. The goal of this study was to compare the reproductive toxic effects of TBBPA and TCBPA on male Rana nigromaculata and to expound on the mechanisms leading to these effects. Healthy adult frogs were exposed to 0, 0.001, 0.01, 0.1, and 1 mg/L of TBBPA and TCBPA for 14 days. Sperm numbers were counted by erythrometry. Sperm mobility and deformities were observed under a light microscope (400 ×). We used commercial ELISA kits to determine the serum content of testosterone (T), estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Expression of androgen receptor (AR) mRNA was detected using real-time qPCR. Sperm numbers and sperm mobility were significantly decreased and sperm deformity was significantly increased in a concentration dependent manner following exposure to TBBPA and TCBPA. Sperm deformity was significantly greater in the 1 mg/L TCBPA (0.549) treatment group than in the 1 mg/L TBBPA (0.397) treatment group. Serum T content was significantly greater in the 0.01, 0.1 and 1 mg/L TBBPA and TCBPA experimental groups compared with controls, while E2 content was significantly greater in only the 1 mg/L TBBPA and TCBPA experimental groups. Expression levels of LH and FSH significantly decreased in the 1 mg/L TBBPA and TCBPA treatment groups. AR mRNA expression decreased markedly in all the treated groups. Our results indicated that TBBPA and TCBPA induced reproductive toxicity in a dose-dependent manner, with TCBPA having greater toxicity than TBBPA. Furthermore, changes in T, E2, LH, and FSH levels induced by TBBPA and TCBPA exposure, which led to endocrine disorders, also caused disturbance of spermatogenesis through abnormal gene expressions of AR in the testes.
اظهر المزيد [+] اقل [-]Estrogenic potency of MC-LR is induced via stimulating steroidogenesis: In vitro and in vivo evidence
2018
Hou, Jie | Su, Yujing | Lin, Wang | Guo, Honghui | Li, Li | Anderson, Donald M. | Li, Dapeng | Tang, Rong | Chi, Wei | Zhang, Xi
Waterborne microcystin-LR (MC-LR) has been reported to disrupt sex hormones, while its estrogenic potency remains controversial. We hypothesized that MC-LR could induce estrogenic effects via disrupting sex hormone synthesis, and verified this hypothesis by in vitro and in vivo assays. Effects of MC-LR (1, 10, 100, 500, 1000 and 5000 μg/L) on steroidogenesis were assessed in the H295R cells after 48 h. The contents of 17β-estradiol (E2) and testosterone (T) increased in a non-dose-dependent manner, which showed positive correlations with the expression of steroidogenic genes. In the in vivo assay, adult male zebrafish were exposed to 0.3, 1, 3, 10 and 30 μg/L MC-LR for 30 d. Similarly, E2 and T contents in the testis were increased, accompanied by extensive up-regulation of steroidogenic genes, especially cyp19a. Meanwhile, the percentage of spermatid in the testis declined. In the liver, the vtg1 gene was significantly up-regulated while both the transcriptional and protein levels of the estrogenic receptor (ER) declined. These results indicate that MC-LR induced non-dose-dependent estrogenic effects at environmental concentrations, which may result from steroidogenesis stimulation via a non-ER-mediated pathway. Our findings support a paradigm shift in the risk assessment of MC-LR from traditional toxicity to estrogenic risk, particularly at low concentrations, and emphasize the potential threat to the male reproductive capacity of wildlife in bloom areas.
اظهر المزيد [+] اقل [-]Reproductive toxicity of azoxystrobin to adult zebrafish (Danio rerio)
2016
Cao, Fangjie | Zhu, Lizhen | Li, Hui | Yu, Song | Wang, Chengju | Qiu, Lihong
In the past few decades, extensive application of azoxystrobin has led to great concern regarding its adverse effects on aquatic organisms. The objective of the present study was to evaluate the reproductive toxicity of azoxystrobin to zebrafish. After adult zebrafish of both sexes were exposed to 2, 20 and 200 μg/L azoxystrobin for 21 days, egg production, the fertilization rate, the gonadosomatic index (GSI) and hepatosomatic index (HSI), 17β-estradiol (E2), testosterone (T) and vitellogenin (Vtg) concentrations, and histological alterations in the gonads and livers were measured. Meanwhile, expression alterations of genes encoding gonadotropins and gonadotropin receptors (fshb, lhb, fshr and lhr), steroid hormone receptors (era, er2b and ar), steroidogenic enzymes (cyp11a, cyp11b, cyp17, cyp19a, cyp19b, hsd3b and hsd17b) in the hypothalamic-pituitary-gonad (HPG) axis and vitellogenin (vtg1 and vtg2) in the livers were also investigated. The results showed that reduced egg production and fertilization rates were observed at 200 μg/L azoxystrobin. In female zebrafish, reduced E2 and Vtg concentrations, decreased GSI, increased T concentrations, and histological alterations in the ovaries and livers were observed at 200 μg/L azoxystrobin, along with significant down-regulation of lhb, cyp19b, lhr, cyp19a, vtg1 and vtg2, and up-regulation of cyp17, hsd3b and hsd17b. In male zebrafish, increased E2 and Vtg concentrations, reduced T concentration and GSI, and histological alterations in the testes and livers were observed after exposure to 20 and 200 μg/L azoxystrobin, along with significant up-regulations of cyp19b, cyp11a, cyp17, cyp19a, hsd3b and hsd17b, vtg1 and vtg2. Moreover, cyp11a, hsd3b, cyp19a, vtg1 and vtg2 in male zebrafish were significantly up-regulated after treatment with 2 μg/L azoxystrobin. The results of the present study indicate that azoxystrobin led to reproductive toxicity in zebrafish and male zebrafish were more sensitive to azoxystrobin than female zebrafish.
اظهر المزيد [+] اقل [-]