REPRODUCTIVE TOXICOLOGY
·
2025
·
IF 2.8
Huage Liu
Thirdhand smoke (THS), a residual cigarette smoke still remaining in indoor environment long after active smoking has ceased, has aroused more and more people’s attention on health. However, the impact of THS exposure on the male reproductive system, particularly in in-vivo study, remain unclear. Thus, this study aims to investigate the adverse effects of 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA), a special component in THS, on testis. Herein, adult ICR mice were orally administered diluted dimethylsulfoxide (control), 0.075 μg/kg and 0.15 μg/kg NNA for 10 weeks. The findings revealed that NNA exposure, especially in 0.15 μg/kg dosage, significantly reduced the epithelium height and tubular area within the testis. Transcriptomic analysis indicated that NNA exposure interfered with the expression of genes associated with oxygen transport and oxygen binding processes, such as Hbb-bs , the downregulation of which also led to oxidative damage. Additionally, NNA exposure induced oxidative damage in testis by decreased levels of SOD and GSH enzymes, along with an increase in MDA level. In summary, our results demonstrate that NNA exposure causes impaired testicular structure and oxidative damage, indicating its testicular toxicity. This finding not only implies the detrimental effect of NNA on male reproduction, but also provides a fundamental basis for further research on the impact of THS exposure on male reproductive health.
研究领域:
毒理学
·
生殖健康
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2012
·Vol. 7
·期 9
·e44754
·
IF 4.092
Minjian Chen,Bin Xu,Wenliang Ji,Shanlei Qiao,Nan Hu,Yanhui Hu,Wei Wu,Lianglin Qiu,Ruyang Zhang,Yubang Wang,Shoulin Wang,Zuomin Zhou,Yankai Xia,Xinru Wang
Background
Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction.
Methodology/Principal Findings
Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group.
Conclusions/Significance
BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity.
研究领域:
毒理学
·
生殖健康
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2020
·
IF 4.679
Zengqiang Li,Yige Yu,Yang Li,Feifei Ma,Yinghui Fang,Chaobo Ni,Keyang Wu,Peipei Pan,Ren-Shan Ge
Di-n-butyl phthalate (DBP) is widely used in consumer products as a plasticizer . Here, we report a natural product taxifolin that can attenuate developmental and reproductive toxicity of DBP. Pregnant rats were daily gavaged with 500 mg/kg DBP alone or together with taxifolin (10 and 20 mg/kg) from gestational day (GD) 12–21. At GD21, sera and testes of male fetus were collected. DBP significantly lowered serum testosterone level at 500 mg/kg and taxifolin can completely reverse its action. DBP caused abnormal aggregation of fetal Leydig cells and taxifolin can reverse it. DBP down-regulated the expression of the genes of cholesterol side-chain cleavage enzyme ( Cyp11a1 ), 17β-hydroxysteroid dehydrogenase 3 ( Hsd17b3 ), and insulin-like 3 ( Insl3 ) and taxifolin can reverse its action. DBP increased malondialdehyde levels and decreased superoxide dismutase and glutathione peroxidase expression and taxifolin can reverse it. DBP increased incidence of multinucleated gonocytes and taxifolin can prevent it. Moreover, DBP lowered sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and phosphorylated AMP-activated protein kinase (pAMPK) signalling and taxifolin antagonized DBP. In conclusion, in utero exposure to DBP caused developmental/reproductive toxicity of male offspring via increasing reactive oxygen species and taxifolin is an effective food component that completely reverses DBP-mediated action.
研究领域:
毒理学
·
生殖健康
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2023
·
IF 3.5
Zhang Qian,Chuwei Li,Wei Zhao,Zhaowanyue He,Mengqi Xue,Shuxian Wang,Xi Cheng,Rujun Ma,Xie Ge
As a widespread environmental contaminant, short chain chlorinated paraffins (SCCPs) has attracted great attention. However, the toxicity of SCCPs on male reproductive system remains ambiguous. In this study, we treated mice with SCCPs by gavage and investigated the toxic effects of SCCPs on testis . According to the results, the sperm parameters of mice were significantly reduced after exposure to 1, 10, 100 mg/kg body mass per day SCCPs for 35 days. SCCPs resulted in disorderly arranged seminiferous epithelium and increased apoptotic cells in testes. Both in vivo and in vitro experiments indicated that the oxidative stress was induced after SCCPs exposure, and dysfunction of nuclear factor erythroid-related factor (NRF2) signaling pathway played a role in this process. Moreover, resveratrol , an NRF2 activator, could alleviate the damage of SCCPs onmale reproductive system. Our study indicated that oxidative stress is the key point for explaining the testicular toxicity caused by SCCPs, and NRF2 could be used as a potential target for clinical treatment to alleviate the reproductive toxicity induced by SCCPs.
研究领域:
环境毒理学
·
生殖生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2018
·Vol. 187
·期 1
·281-290
·
IF 2.361
Wang Hongmei,Zhang Ruili,Song Yangyang,Li Tianqi,Ge Ming
Studies have shown that cadmium can cause chicken testicular damage, but a protective effect of Ganoderma triterpenoids on cadmium-induced testicular damage in chickens has not yet been reported. The present study was designed to research the protective effect of Ganoderma triterpenoids on cadmium-induced testicular damage in chicken. Eighty healthy 7-day-old Hyline egg laying chickens were randomly divided into four groups with 20 in each group. The control group was fed with normal full-fodder, the model group was fed with normal full-fodder with 140 mg/kg of CdCl 2 , the Ganoderma triterpenoid treatment group was fed with a full-fodder diet containing 140 mg/kg of CdCl 2 and 0.5 mL of Ganoderma triterpenoid solution (20 mg/mL), and the Ganoderma triterpenoid group was fed normal full-fodder and 0.5 mL of Ganoderma triterpenoid solution (20 mg/mL) gavage. The chickens were euthanized at 20, 40, and 60 days, respectively, and the testes were harvested. The changes of cadmium contents, the antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), peroxide (malondialdehyde (MDA)), inflammatory factors (interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)), and apoptosis-related proteins (Bax, Bcl-2, and Caspase-3) were detected. The pathological sections of the testes were made at the same time. The results suggested that Ganoderma triterpenoids could reduce the accumulation of cadmium in testis tissue; reduce the content of IL-1β, IL-6, and TNF-α in cadmium poisoning testis; significantly increase the activity of SOD and GSH-Px; decrease the content of MDA; regulate the expression of Bax, Caspase-3, and Bcl-2; and reduce the damage of testicular tissue. The results showed that Ganoderma triterpenoids have a protective effect on cadmium-induced testicular injury in chicken.
研究领域:
兽医学
·
毒理学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Yifan Hong,Xiazhu Zhou,Qi Li,Jing Chen,Yuexin Wei,Siyuan Wang,Xiangqin Zheng,Jie Zhao,Chengjun Yu,Jun Pei,Jie Zhang,Chunlan Long,Lianju Shen,Shengde Wu,Guanghui Wei
Di (2-ethylhexyl) phthalate (DEHP), one of phthalic acid esters, has been widely used in daily products. Its main metabolite, mono (2-ethylhexyl) phthalate (MEHP) was reported to possess higher testicular toxicity than DEHP. To explore the precise mechanism in MEHP-induced testis damage, multiple transcriptomic sequencing was employed in spermatogonia cell line GC-1 cells treated with MEHP (0, 100, and 200 μM) for 24 h. Integrative omics analysis and empirical validation revealed that Wnt signaling pathway was downregulated and wnt10a , one of hub genes, may be the key player in this process. Similar results were observed in DEHP-exposed rats. MEHP-induced disturbance of self-renewal and differentiation was dose-dependent. Moreover, self-renewal proteins were downregulated; the differentiation level was stimulated. Meanwhile, GC-1 proliferation was decreased. Stable transformation strain of wnt10a overexpression GC-1 cell line constructed from lentivirus was utilized in this study. The upregulation of Wnt10a significantly reversed the dysfunction of self-renewal and differentiation and promoted the cell proliferation. Finally, retinol, predicted to be useful in CONNECTIVITY MAP (cMAP), failed to rescue the damage caused by MEHP. Cumulatively, our findings revealed that the downregulation of Wnt10a induced the imbalance of self-renew and differentiation, and inhibition of cell proliferation in GC-1 cells after MEHP exposure.
研究领域:
毒理学
·
分子生物学
·
细胞生物学
·
生殖生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2024
·
IF 10.3
Bingli Zhang,Yizhou Zhong,Jiaxin Du,Rongyi Ye,Bingchi Fan,Yanhong Deng,Ruobing Bai,Yu Feng,Xiaohong Yang,Yuji Huang,Boxuan Liang,Jiewei Zheng,Weifeng Rong,Xingfen Yang,Zhenlie Huang
1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and lactate dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular pyroptosis, and overexpression of piR-mmu-1019957 did not promote pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.
研究领域:
环境毒理学
·
生殖生物学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Shi-Long Ruan,Lei Xie,Jun-Wei Ou,Xue-Song Sun,Yong-Pu Zhang,Jian-Rao Hu
Cadmium (Cd) is an environmental toxicant and a nonessential metal. Cd can attack a wide range of organs, such as the liver, kidney, lung, ovary, testis, brain, and muscle in vertebrates. Among these organs, the testis might be the most sensitive organ to Cd toxicity. Metallothionein (MT) is a cysteine-rich protein with a low molecular weight, that can bind with Cd and eliminate reactive oxygen species (ROSs). Hydrogen peroxide, which as a crucial type of ROS that is induced by Cd, can be eliminated by catalase (CAT) in the self-protection of cells and to realize Cd toxicity resistance. To investigate the functions of MT and CAT in the testis of Cynops orientalis , we cloned the full-length MT and CAT genes of C. orientalis for the first time. Immunofluorescence results demonstrated that MT and CAT were expressed in Sertoli cells and all spermatogenic cells in the testis of C. orientalis . The results of the ultrastructural damage assay demonstrated that there were various impairments, which included organelle vacuolization, abnormal chromatin distribution, and apoptotic bodies, in somatic cells that were exposed to Cd. However, the anomalies of spermatozoa were located mainly in the mid-piece and head, many of which showed severely impaired structures. The results demonstrated that MT and CAT expression had distinct patterns in response to various Cd concentrations: an increase in MT mRNA levels with elevated Cd levels and a persistent increase in CAT mRNA levels with elevated Cd levels. These results suggested that MT and CAT play roles in Cd toxicity resistance in the testis and that the expression of CAT may be a better biomarker than the expression of MT for assessing Cd pollution.
研究领域:
环境毒理学
·
分子生物学
·
生殖生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
IF 3.571
Zhongfei Zhang,Puyu Yang,Boyan Gao,Guoren Huang,Man Liu,Liangli Lucy Yu
A novel synthetic route was designed, developed, and utilized to synthesize six high-purity 2-monochloropropanediol fatty acid esters (2-MCPD esters), a group of potential processing-induced food contaminants. A chlorine atom was introduced to C-2 of a diethyl malonate molecule, which was reduced by NaBH4 and followed by esterification using fatty acids. The reaction products were isolated and purified using silica gel columns to obtain three 2-MCPD monoesters and three diesters at about 50–54% and 56–59% yields, respectively. In addition, 2-MCPD monopalmitate and dipalmitate were examined for their acute oral toxicities in Swiss mice. The LD50 values of 2-MCPD mono- and dipalmitate were greater than 5000 mg/kg body weight (BW), along with detectable nephrotoxicity and testicular toxicity. The results of this study may promote future investigation of MCPD ester toxicology and detection.
研究领域:
食品科学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Wei Guangji,Peng Huixin,Hu Hongfei,Lan Hai,Feng Yang,Luo Shihua,Huang Yanxin,Yuan Huixiong,Chen Wencheng
Aluminum (Al) is a pervasive environmental contaminant with detrimental biological effects. Although Al exposure induces oxidative stress and toxicity in spermatogenic cells, leading to impaired male reproductive function, the underlying molecular mechanisms remain incompletely elucidated. In this study, we systematically evaluated the toxic effects of Al on spermatogenic cells using both in vivo and in vitro models. Transcriptomic profiling of GC-2spd cells revealed Al-induced differential gene expression related to oxidative stress response, iron homeostasis, and lipid metabolism regulation. These alterations were notably enriched in the ferroptosis and HIF-1 signaling pathways. Subsequent in vivo analyses demonstrated that Al exposure increased iron levels and oxidative stress while reducing ATP content in mouse testes, resulting in testicular damage, decreased sperm quality, and lowered serum sex hormone levels, all of which contribute to reproductive dysfunction. Further investigations confirmed that Al disrupts redox and iron homeostasis, promoting lipid peroxidation and ferroptosis in both mouse testes and GC-2spd cells. Importantly, administration of the ferroptosis inhibitor Ferrostatin-1 (Fer-1) effectively restored homeostasis, thereby alleviating Al-induced ferroptosis and spermatogenic cell toxicity. In conclusion, this study demonstrates that Al disrupts iron and redox balance, leading to iron accumulation and lipid peroxidation in spermatogenic cells, which triggers ferroptosis and ultimately causes male reproductive impairment. These findings identify ferroptosis as a novel therapeutic target for mitigating aluminum-related reproductive risks and provide a scientific basis for public health interventions in occupational and environmental settings grounded in this newly characterized cell death mechanism.
研究领域:
毒理学
·
生殖生物学
·
分子细胞生物学
·
环境医学
·
氧化应激
·
金属毒理
·
细胞死亡机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2021
·Vol. 200
·期 6
·2825-2837
·
IF 3.738
Meng Xiaojia,Li Li,An Hongmei,Deng Yaxin,Ling Chunmei,Lu Tianjiao,Song Guanling,Wang Yan
Purpose The research was carried out to investigate the possible ameliorative effect of lycopene on TiO 2 NPs-induced male reproductive toxicity and explore the possible mechanism. Methods Ninety-six healthy male Institute of Cancer Research (ICR) mice were equally divided into eight groups (control group, 50 mg/kg TiO 2 NPs group, 5 mg/kg LYC group, 20 mg/kg LYC group, 40 mg/kg LYC group, 50 mg/kg TiO 2 NPs + 5 mg/kg LYC group, 50 mg/kg TiO 2 NPs + 20 mg/kg LYC group, 50 mg/kg TiO 2 NPs + 40 mg/kg LYC group), and the mice were treated by intragastric administration every day for 30 days in this research. Sperm parameters, testicular histopathology, oxidant and antioxidant enzymes, and cell apoptosis-related protein expression in the testicular tissue were analyzed. Results The results showed that TiO 2 NPs exposure significantly decreased sperm count and motility, and TiO 2 NPs also increased sperm malformation in the epididymis; these characteristics were improved when co-administration with LYC. Testicular histopathological lesions like disorder of germ cells arrange, detachment, atrophy, and vacuolization were observed after TiO 2 NPs exposure, and these abnormalities were effectively ameliorated by co-administration with LYC. Oxidative stress was induced by TiO 2 NPs exposure as evidenced by increased the level of MDA and decreased the activity of SOD as well as the level of anti-O 2 − , and these alterations were effectively prevented by co-administration with LYC. LYC also alleviated TiO 2 NPs-induced germ cell apoptosis by inhibiting mitochondrial apoptotic pathway, as shown by the upregulation of Bcl-2, the downregulation of Bax, Cleaved Caspase 3, and Cleaved Caspase 9. Conclusion LYC could ameliorate TiO 2 NPs-induced testicular damage via inhibiting oxidative stress and apoptosis, which could be used to alleviate the testicular toxicity associated with TiO 2 NPs intake.
研究领域:
毒理学
·
生殖生物学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 24
·12256-12264
·
IF 5.396
Yi Zhao,Ling-Ge Cui,Milton Talukder,Jia-Gen Cui,Hao Zhang,Jin-Long Li
Lycopene (LYC) is a potent antioxidant synthesized by red vegetables or plants. Di-2-ethylhexyl phthalate (DEHP) is frequently detected in diverse agricultural environments and considered as a reproductive toxicant. The present research was designed to assess the potential mechanisms of DEHP-induced testicular toxicity and the treatment efficacy of LYC. In this study, after the oral administration of LYC at the dose of 5 mg per kg b.w. per day, mice were given 500 or 1000 mg per kg b.w. per day of DEHP. This research suggested that LYC prevented the DEHP-induced disorder at the levels of activity and content of CYP450 enzymes. LYC attenuated DEHP-caused enhancement in nuclear xenobiotic receptors (NXRs) and the phase I metabolizing enzymes (CYP1, CYP2, CYP3, etc.) levels. Furthermore, endoplasmic reticulum (ER) stress was induced by DEHP and triggered unfolded protein response (UPR). Interestingly, LYC could effectively ameliorate these “hit”. The present study suggested that LYC prevents DEHP-induced ER stress in testis via regulating NXRs and UPRER.
研究领域:
毒理学
·
生殖生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）