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Haitao Gao - One of the best experts on this subject based on the ideXlab platform.

  • zinc supplement ameliorates phthalates induced Reproductive Toxicity in Male rats
    Chemosphere, 2020
    Co-Authors: Haitao Gao, Liangliang Qian, Weixin Cao
    Abstract:

    Abstract People are inevitably exposed to phthalates (PEs) ubiquitously existing in environment. Our previous studies, simulating the actual situations of people exposure to PEs, have shown that the sub-chronic exposure to low-doses PEs mixture (MIXPs) impaired Reproductive function in Male rats. Zinc is an important element in maintaining Male Reproductive functions. However, it is still unknown whether zinc supplement could mitigate PEs-induced Male Reproductive Toxicity or not with sub-chronic low-dose mixture exposure. This study aimed to explore the effect of zinc supplement on the Reproductive Toxicity caused by sub-chronic MIXPs exposure (160 mg/(kg•body weight)/d, for 90 days) in Male rats, and further to reveal the underlying mechanisms. Testosterone (T), FSH and LH in serum, early Toxicity indicators in urine, PIWI proteins (PIWIL1 and PIWIL2) expression in testes and pathological examination were performed for Toxicity evaluation. Steroidogenic proteins (17β-HSD, StAR, CYP17A1, P450scc and SRD5A) were measured for mechanisms of exploration. The results indicated that zinc supplement could inhibit the T, LH, FSH level decreases in serum, abolish the effect of 5 early Toxicity indicators’ levels in urine, restrain the alteration of PIWI proteins expression and improve the constructional injury of testes. These effects might be relevant with the suppressed alteration of the expression of steroidogenic proteins induced by MIXPs in rat testicular cells. This work may offer further insights into reducing health risks of MIXPs exposure.

  • determination of five sex hormones in urine samples for early evaluation of Male Reproductive Toxicity induced by phthalate esters in rats
    Journal of Agricultural and Food Chemistry, 2018
    Co-Authors: Liangliang Qian, Haitao Gao, Chunmin Wang
    Abstract:

    In this work, Male rats were exposed to multiple phthalate esters (MIXPs) in a long-term low-dose model for the early evaluation of Reproductive Toxicity. An ananlysis method with better sensitivity, accuracy and precision was established to determine the five sex hormones (androstenedione, testosterone, dehydroepiandrosterone, dihydrotestosterone, and estrone) in collected urine samples. The results showed that all the analytes in the MIXPs treated group changed in a time-dependent manner. Specifically, estrone significantly decreased from the 30th day and the other four changed from the 30th day and then significantly increased on the 60th day, while no obvious changes were found in the control group. Therefore, a possible way was provided for the early evaluation of Male Reproductive Toxicity induced by Phthalate esters (PEs) . The reliability of judgment was improved by observing the changes of five target hormones simultaneously. Furthermore, good compliance was predicted for the practical application due to the noninvasive and convenient urine sample collection.

  • effects of six priority controlled phthalate esters with long term low dose integrated exposure on Male Reproductive Toxicity in rats
    Food and Chemical Toxicology, 2017
    Co-Authors: Haitao Gao, Weixin Cao, Liangliang Qian, Min Wang
    Abstract:

    Human beings are inevitably exposed to ubiquitous phthalate esters (PEs) surroundings. The purposes of this study were to investigate the effects of long-term low-dose exposure to the mixture of six priority controlled phthalate esters (MIXPs): dimethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DBP), butyl benzyl phthalate (BBP), di(2-ethyhexyl) phthalate (DEHP) and di-n-octyl phthalate (DNOP), on Male rat Reproductive system and further to explore the underlying mechanisms of the Reproductive Toxicity. The Male rats were orally exposed to either sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses by gavage for 15 weeks. Testosterone and luteinizing hormone (LH) in serum were analyzed, and pathological examinations were performed for Toxicity evaluation. Steroidogenic proteins (StAR, P450scc, CYP17A1 and 17β-HSD), cell cycle and apoptosis-related proteins (p53, Chk1, Cdc2, CDK6, Bcl-2 and Bax) were measured for mechanisms exploration. MIXPs with long-term low-dose exposure could cause Male Reproductive Toxicity to the rats, including the decrease of both serum and testicular testosterone, and the constructional damage of testis. These effects were related to down-regulated steroidogenic proteins, arresting cell cycle progression and promoting apoptosis in rat testicular cells. The results indicate that MIXPs with long-term low-dose exposure may pose Male Reproductive Toxicity in human.

Fenju Qin - One of the best experts on this subject based on the ideXlab platform.

  • sf 1 mediates Reproductive Toxicity induced by cerium oxide nanoparticles in Male mice
    Journal of Nanobiotechnology, 2019
    Co-Authors: Jie Zhang, Fenju Qin, Tao Shen, Junchao Qian, Guangming Zhou, Jian Tong
    Abstract:

    Cerium oxide nanoparticles (CeO2 NPs) have potential application for use in biomedical and in various consumer products. However, it is largely unclear whether CeO2 NPs have effects on Male Reproductive function. In this study, Male mice were examined for Toxicity, if any, following chronic oral administration of CeO2 NPs for 32 days. In each animal, epididymides were examined for sperm motility and DNA integrity. Bloods were tested for testosterone levels. Testicular tissues were collected to determine the element Ce content, the daily sperm production (DSP), marker enzymes such as ACP, G6PD, γ-GT and SDH, mRNA expression levels of steroidogenesis genes Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as steroidogenic factor-1 (SF-1) gene/protein levels. The results showed that CeO2 NPs (20 mg/kg and 40 mg/kg) increased the element Ce content in testis, the testis histopathological patterns and sperm DNA damage whereas decreased the testis weight, DSP and sperm motility. There were also remarkable reduction in testosterone levels and marker enzymes activities, down-regulated mRNA expression levels of several steroidogenesis genes such as Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as altered gene and protein expressions of SF-1. These results reveal the Male Reproductive Toxicity of chronic exposure of CeO2 NPs in mice, hinting that the utilization of CeO2 NPs need to be carefully evaluated about their potential Reproductive Toxicity on the human health.

  • SF-1 mediates Reproductive Toxicity induced by Cerium oxide nanoparticles in Male mice
    'Springer Science and Business Media LLC', 2019
    Co-Authors: Fenju Qin, Jie Zhang, Tao Shen, Junchao Qian, Guangming Zhou, Jian Tong
    Abstract:

    Abstract Background Cerium oxide nanoparticles (CeO2 NPs) have potential application for use in biomedical and in various consumer products. However, it is largely unclear whether CeO2 NPs have effects on Male Reproductive function. Methods In this study, Male mice were examined for Toxicity, if any, following chronic oral administration of CeO2 NPs for 32 days. In each animal, epididymides were examined for sperm motility and DNA integrity. Bloods were tested for testosterone levels. Testicular tissues were collected to determine the element Ce content, the daily sperm production (DSP), marker enzymes such as ACP, G6PD, γ-GT and SDH, mRNA expression levels of steroidogenesis genes Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as steroidogenic factor-1 (SF-1) gene/protein levels. Results The results showed that CeO2 NPs (20 mg/kg and 40 mg/kg) increased the element Ce content in testis, the testis histopathological patterns and sperm DNA damage whereas decreased the testis weight, DSP and sperm motility. There were also remarkable reduction in testosterone levels and marker enzymes activities, down-regulated mRNA expression levels of several steroidogenesis genes such as Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as altered gene and protein expressions of SF-1. Conclusion These results reveal the Male Reproductive Toxicity of chronic exposure of CeO2 NPs in mice, hinting that the utilization of CeO2 NPs need to be carefully evaluated about their potential Reproductive Toxicity on the human health

Jie Zhang - One of the best experts on this subject based on the ideXlab platform.

  • sf 1 mediates Reproductive Toxicity induced by cerium oxide nanoparticles in Male mice
    Journal of Nanobiotechnology, 2019
    Co-Authors: Jie Zhang, Fenju Qin, Tao Shen, Junchao Qian, Guangming Zhou, Jian Tong
    Abstract:

    Cerium oxide nanoparticles (CeO2 NPs) have potential application for use in biomedical and in various consumer products. However, it is largely unclear whether CeO2 NPs have effects on Male Reproductive function. In this study, Male mice were examined for Toxicity, if any, following chronic oral administration of CeO2 NPs for 32 days. In each animal, epididymides were examined for sperm motility and DNA integrity. Bloods were tested for testosterone levels. Testicular tissues were collected to determine the element Ce content, the daily sperm production (DSP), marker enzymes such as ACP, G6PD, γ-GT and SDH, mRNA expression levels of steroidogenesis genes Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as steroidogenic factor-1 (SF-1) gene/protein levels. The results showed that CeO2 NPs (20 mg/kg and 40 mg/kg) increased the element Ce content in testis, the testis histopathological patterns and sperm DNA damage whereas decreased the testis weight, DSP and sperm motility. There were also remarkable reduction in testosterone levels and marker enzymes activities, down-regulated mRNA expression levels of several steroidogenesis genes such as Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as altered gene and protein expressions of SF-1. These results reveal the Male Reproductive Toxicity of chronic exposure of CeO2 NPs in mice, hinting that the utilization of CeO2 NPs need to be carefully evaluated about their potential Reproductive Toxicity on the human health.

  • SF-1 mediates Reproductive Toxicity induced by Cerium oxide nanoparticles in Male mice
    'Springer Science and Business Media LLC', 2019
    Co-Authors: Fenju Qin, Jie Zhang, Tao Shen, Junchao Qian, Guangming Zhou, Jian Tong
    Abstract:

    Abstract Background Cerium oxide nanoparticles (CeO2 NPs) have potential application for use in biomedical and in various consumer products. However, it is largely unclear whether CeO2 NPs have effects on Male Reproductive function. Methods In this study, Male mice were examined for Toxicity, if any, following chronic oral administration of CeO2 NPs for 32 days. In each animal, epididymides were examined for sperm motility and DNA integrity. Bloods were tested for testosterone levels. Testicular tissues were collected to determine the element Ce content, the daily sperm production (DSP), marker enzymes such as ACP, G6PD, γ-GT and SDH, mRNA expression levels of steroidogenesis genes Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as steroidogenic factor-1 (SF-1) gene/protein levels. Results The results showed that CeO2 NPs (20 mg/kg and 40 mg/kg) increased the element Ce content in testis, the testis histopathological patterns and sperm DNA damage whereas decreased the testis weight, DSP and sperm motility. There were also remarkable reduction in testosterone levels and marker enzymes activities, down-regulated mRNA expression levels of several steroidogenesis genes such as Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as altered gene and protein expressions of SF-1. Conclusion These results reveal the Male Reproductive Toxicity of chronic exposure of CeO2 NPs in mice, hinting that the utilization of CeO2 NPs need to be carefully evaluated about their potential Reproductive Toxicity on the human health

  • integrated proteomics and metabolomics analysis of rat testis mechanism of arsenic induced Male Reproductive Toxicity
    Scientific Reports, 2016
    Co-Authors: Qingyu Huang, Lianzhong Luo, Ambreen Alamdar, Jie Zhang, Liangpo Liu, Meiping Tian, Syed Ali Musstjab Akber Shah Eqani, Heqing Shen
    Abstract:

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced Male Reproductive Toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to Male Reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these Male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced Male Reproductive Toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

Elaine M Faustman - One of the best experts on this subject based on the ideXlab platform.

  • the presence of macrophages and inflammatory responses in an in vitro testicular co culture model of Male Reproductive development enhance relevance to in vivo conditions
    Toxicology in Vitro, 2016
    Co-Authors: Sean M Harris, Sungwoo Hong, Sara Pacheco Shubin, Susanna Wegner, Kirk P Van Ness, Foad Green, Elaine M Faustman
    Abstract:

    Our 3-dimensional testis co-culture system (3D-TCS) represents a promising model of Male Reproductive Toxicity which captures sensitive processes of Male Reproductive development and contains the main testes cell types (germ, Leydig and Sertoli cells). Macrophages are another cell type important for testicular function and help to modulate immuno-endocrine processes during testes development. Chemicals such as phthalate esters (PE's) affect macrophage function and testosterone production in the testes in vivo. The aim of this study was to determine whether macrophages were present in the 3D-TCS and investigate responses in our model that may be related to immuno-endocrine functions. We observed consistent expression of the resident macrophage marker ED2 as well as increases in inflammatory cytokines produced by macrophages and testes cells (IL-6, TNF-α and KC/GRO) after exposure to toxic PE's. Pathway analysis of gene expression changes after exposure to PE's showed that IL-6 and TNF-α signaling pathways were enriched after treatment with Reproductively toxic, but not non-Reproductively toxic phthalates. These results indicate that macrophages and inflammatory processes are captured in the 3D-TCS and that these processes are impacted by exposure to Reproductive toxicants. These processes represent a major mode of action for in vivo testis Toxicity for a variety of compounds and our novel in vitro model is able to capture toxicant perturbation of immune function.

  • improving in vitro sertoli cell gonocyte co culture model for assessing Male Reproductive Toxicity lessons learned from comparisons of cytoToxicity versus genomic responses to phthalates
    Toxicology and Applied Pharmacology, 2009
    Co-Authors: Sungwoo Hong, Estefania G Moreira, Elaine M Faustman
    Abstract:

    Gonocytes exist in the neonatal testis and represent a transient population of Male germ-line stem cells. It has been shown that stem cell self-renewal and progeny production is probably controlled by the neighboring differentiated cells and extracellular matrix (ECM) in vivo known as niches. Recently, we developed an in vitro three-dimensional (3D) Sertoli cell/gonocyte co-culture (SGC) model with ECM overlay, which creates an in vivo-like niche and supports germ-line stem cell functioning within a 3D environment. In this study, we applied morphological and cytoToxicity evaluations, as well as microarray-based gene expression to examine the effects of different phthalate esters (PE) on this model. Known in vivo Male developmentally toxic PEs (DTPE) and developmentally non-toxic PEs (DNTPE) were evaluated. We observed that DTPE induced significantly greater dose-dependent morphological changes, a decrease in cell viability and an increase in cytoToxicity compared to those treated with DNTPE. Moreover, the gene expression was more greatly altered by DTPE than by DNTPE and non-supervised cluster analysis allowed the discrimination of DTPE from the DNTPE. Our systems-based GO-Quant analysis showed significant alterations in the gene pathways involved in cell cycle, phosphate transport and apoptosis regulation with DTPE but not with DNTPE treatment. Disruptions of steroidogenesis related-gene expression such as Star, Cyp19a1, Hsd17b8, and Nr4a3 were observed in the DTPE group, but not in the DNTPE group. In summary, our observation on cell viability, cytoToxicity, and microarray-based gene expression analysis induced by PEs demonstrate that our in vitro 3D-SGC system mimicked in vivo responses for PEs and suggests that the 3D-SGC system might be useful in identifying developmental Reproductive toxicants.

  • essential role of extracellular matrix ecm overlay in establishing the functional integrity of primary neonatal rat sertoli cell gonocyte co cultures an improved in vitro model for assessment of Male Reproductive Toxicity
    Toxicological Sciences, 2005
    Co-Authors: Xiaozhong Yu, Sungwoo Hong, Jaspreet S Sidhu, Elaine M Faustman
    Abstract:

    The development of in vitro models for testicular Toxicity may provide important tools for investigating specific mechanisms of Toxicity in the testis. Although various systems have been reported, their application in toxicological studies has been limited by the poor ability to replicate the complex biochemical, molecular, and functional interactions observed in the testis. In the present study, we evaluated a significantly improved Sertoli cell/gonocyte co-culture (SGC) system that employs a 3dimensional extracellular matrix Matrigel (ECM) applied as an overlay instead of a substratum. We explored the dose- and timedependent effects of the addition of such an ECM overlay on cytoskeletal and morphological changes in the SGC system, and the resulting effects on cellular integrity. Furthermore, we correlated the latter effects with the ECM-dependent modulation of stress and survival signaling pathways and, most critically, the expression levels of the spermatogonia-specific protein, c-Kit. Finally, we applied this co-culture system to investigate the doseand time-dependent effects on the morphology and induction of apoptosis of cadmium. We observed that the dose-dependent addition of an ECM overlay led to an enhanced attachment of Sertoli cells and facilitated the establishment of SGC communication and cytoskeletal structure, with a dramatic improvement in cell viability. The latter was consistent with the observed doseand time-dependent modulation of both stress signaling pathways (SAPK/JNK) and survival signaling pathways (ERK and AKT) in the presence of the ECM overlay. Furthermore, the dose-dependent stabilization of c-Kit protein expression confirmed the functional integrity of this co-culture system. We conclude that this modified SGC system will provide investigators with a simple, efficient, and highly reproducible alternative in the screen for testicular cell-specific cytoToxicity and the assessment of molecular mechanisms associated with both normal development and Reproductive Toxicity induced by environmental toxicants.

Jian Tong - One of the best experts on this subject based on the ideXlab platform.

  • sf 1 mediates Reproductive Toxicity induced by cerium oxide nanoparticles in Male mice
    Journal of Nanobiotechnology, 2019
    Co-Authors: Jie Zhang, Fenju Qin, Tao Shen, Junchao Qian, Guangming Zhou, Jian Tong
    Abstract:

    Cerium oxide nanoparticles (CeO2 NPs) have potential application for use in biomedical and in various consumer products. However, it is largely unclear whether CeO2 NPs have effects on Male Reproductive function. In this study, Male mice were examined for Toxicity, if any, following chronic oral administration of CeO2 NPs for 32 days. In each animal, epididymides were examined for sperm motility and DNA integrity. Bloods were tested for testosterone levels. Testicular tissues were collected to determine the element Ce content, the daily sperm production (DSP), marker enzymes such as ACP, G6PD, γ-GT and SDH, mRNA expression levels of steroidogenesis genes Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as steroidogenic factor-1 (SF-1) gene/protein levels. The results showed that CeO2 NPs (20 mg/kg and 40 mg/kg) increased the element Ce content in testis, the testis histopathological patterns and sperm DNA damage whereas decreased the testis weight, DSP and sperm motility. There were also remarkable reduction in testosterone levels and marker enzymes activities, down-regulated mRNA expression levels of several steroidogenesis genes such as Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as altered gene and protein expressions of SF-1. These results reveal the Male Reproductive Toxicity of chronic exposure of CeO2 NPs in mice, hinting that the utilization of CeO2 NPs need to be carefully evaluated about their potential Reproductive Toxicity on the human health.

  • SF-1 mediates Reproductive Toxicity induced by Cerium oxide nanoparticles in Male mice
    'Springer Science and Business Media LLC', 2019
    Co-Authors: Fenju Qin, Jie Zhang, Tao Shen, Junchao Qian, Guangming Zhou, Jian Tong
    Abstract:

    Abstract Background Cerium oxide nanoparticles (CeO2 NPs) have potential application for use in biomedical and in various consumer products. However, it is largely unclear whether CeO2 NPs have effects on Male Reproductive function. Methods In this study, Male mice were examined for Toxicity, if any, following chronic oral administration of CeO2 NPs for 32 days. In each animal, epididymides were examined for sperm motility and DNA integrity. Bloods were tested for testosterone levels. Testicular tissues were collected to determine the element Ce content, the daily sperm production (DSP), marker enzymes such as ACP, G6PD, γ-GT and SDH, mRNA expression levels of steroidogenesis genes Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as steroidogenic factor-1 (SF-1) gene/protein levels. Results The results showed that CeO2 NPs (20 mg/kg and 40 mg/kg) increased the element Ce content in testis, the testis histopathological patterns and sperm DNA damage whereas decreased the testis weight, DSP and sperm motility. There were also remarkable reduction in testosterone levels and marker enzymes activities, down-regulated mRNA expression levels of several steroidogenesis genes such as Star, P450scc, P450c17, 3β-Hsd, and 17β-Hsd, as well as altered gene and protein expressions of SF-1. Conclusion These results reveal the Male Reproductive Toxicity of chronic exposure of CeO2 NPs in mice, hinting that the utilization of CeO2 NPs need to be carefully evaluated about their potential Reproductive Toxicity on the human health