ASIAN JOURNAL OF ANDROLOGY
·
2024
·
IF 3
Zhang Jing-Yi,Yu Xu-Jun,Li Jun-Jun,Xiao Yao,Li Guang-Sen,Yang Fang,Dong Liang
Cuproptosis, a novel mechanism of programmed cell death, has not been fully explored in the context of spermatogenic cells. This study investigated the potential involvement of cuproptosis in spermatogenic cell death using a mouse model of copper overload. Sixty male Institute of Cancer Research (ICR) mice were randomly divided into four groups that received daily oral gavage with sodium chloride (control) or copper sulfate (CuSO 4 ) at 50 mg kg −1 , 100 mg kg −1 , or 200 mg kg −1 , for 42 consecutive days. Mice subjected to copper overload exhibited a disruption in copper homeostasis. Additionally, significant upregulated expression of key cuproptosis factors was accompanied by a significant rise in the rates of testicular tissue cell apoptosis. Immunohistochemical analysis revealed the presence of ferredoxin 1 (Fdx1) in Sertoli cells, Leydig cells, and spermatogenic cells at various stages of testicular development, and the Fdx1-positive staining area was significantly increased in copper-overloaded mice. Mitochondrial dysfunction and decreased adenosine triphosphate levels were also observed, further implicating mitochondrial damage under cuproptosis. Further analyses revealed pathological lesions and blood−testis barrier destruction in the testicular tissue, accompanied by decreased sperm concentration and motility, in copper-overloaded mice. In summary, our results indicate that copper-overloaded mice exhibit copper homeostasis disorder in the testicular tissue and that cuproptosis participates in spermatogenic cell death. These findings provide novel insights into the pathogenic mechanisms underlying spermatogenic cell death and provide initial experimental evidence for the occurrence of cuproptosis in the testis.
研究领域:
生殖生物学
·
毒理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PeerJ
·
2024
·
IF 2.3
Jin Dong,Taowen Ye,Yanli Dong,Jie Hui,Xiaorong Wang
Background Oligospermia is one of the most common reasons for male infertility which is troubling numerous couples of child-bearing age. This investigation scrutinizes the implications and mechanistic underpinnings of ursolic acid’s effect on busulfan-induced oligospermia in mouse models. Methods A singular intraperitoneal injection of busulfan at a dosage of 30 mg/kg induced oligospermia. Two weeks subsequent to this induction, mice were subjected to various dosages of ursolic acid (10, 30, and 50 mg/kg body weight, respectively) on a daily basis for four consecutive weeks. Following this treatment period, a meticulous analysis of epididymal sperm parameters, encompassing concentration and motility, was conducted using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels, including testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde), were gauged employing specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between the oligospermia-induced group and the various ursolic acid treatment groups were identified through RNA sequencing analysis. Results The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice.
研究领域:
生殖生物学
·
药理学
·
分子生物学
·
组织病理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Qiwen Feng,Yumeng Liu,Liping Zou,Mengying Lei,Changhong Zhu,Wei Xia
Fluorene-9-bisphenol (BHPF) is an emerging global endocrine-disrupting chemical found in numerous household products as a substitute of bisphenol A. Many studies have reported various toxicities associated with BHPF. However, the effect of BHPF on male reproduction, particularly on the structural integrity of the blood testis barrier (BTB) in mice, has not yet been extensively studied. Ferroptosis , a newly identified form of cell death, occurs in the testicular tissue following exposure to BPA, affecting male fertility. We investigated whether ferroptosis plays a role in BHPF-induced testicular damage. The findings indicated that BHPF exposure led decreases in serum testosterone (T) concentration and sperm concentration and motility in mice. Furthermore, BHPF disrupted the BTB by interfering with key BTB-related proteins, including Cx43, β-catenin, and ZO-1. Moreover, BHPF induced ferroptosis through the induction of lipid peroxidation, iron overload, oxidative stress , and mitochondrial dysfunction in the testicular tissue. Inhibition of ferroptosis using Fer-1 mitigated the BHPF-induced damage to the BTB and ferroptosis in TM4 cells. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting ferroptosis as a mechanism underlying testicular damage.
研究领域:
毒理学
·
生殖生物学
·
内分泌学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Lirui Hou,Yuhan Fu,Chong Zhao,Lihong Fan,Hongbo Hu,Shutao Yin
Ciprofloxacin (CIP) and enrofloxacin (ENR) are veterinary antibiotics commonly utilized to treat and prevent animal diseases. Environmental and dietary antibiotic residues can directly and indirectly affect the reproductive development of animals and humans. This article investigated the reproductive toxicity of CIP in male zebrafish, showing that it could decrease the spermatogonial weight and damage the spermatogonial tissue. The sex hormone assays showed that CIP decreased fshb and lhb gene expression and plasma testosterone (T). In addition, transcriptome analysis indicated that the effect of CIP on zebrafish might be related to the endocrine signaling pathways. ENR, which was selected for further study, inhibited mouse Leydig (TM3) and Sertoli (TM4) cell proliferation and caused cell cycle arrest. The sperm concentration, serum luteotropic hormone (LH) and follicle-stimulating hormone (FSH), and T levels decreased in adolescent mice after ENR treatment for 30d in vivo. Hematoxylin and eosin (H&E) staining showed that ENR exposure potentially induced testicular injury, while the real-time quantitative PCR (qPCR) results indicated that ENR inhibited the mRNA expression of key genes in the Leydig cells (cyp11a1, 3β-HSD, and 17β-HSD), Sertoli cells (Inhbβ and Gdnf) and spermatogenic cells (Plzf, Stra8 and Dmc1). In conclusion, these findings indicated that ENR exposure might influence the development of the testes of pubescent mice.
研究领域:
兽医学
·
生殖生物学
·
毒理学
·
内分泌学
✓ 已验证
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2024
·
IF 4.4
Zhu Yuan-ting,Wang Xing-jie,Liu Shu-liang,Lai Jing-hui,Li Jian-long,Li Qin,Hu Kai-di,Liu Ai-ping,Yang Yong,He Li,Chen Shu-juan,Ao Xiao-lin,Zou Li-kou
Phthalate acid esters (PAEs) and their metabolites, such as di- n -butyl phthalate (DBP) and mono- n -butyl phthalate (MBP), are known to cause male reproductive damage. Lactiplantibacillus plantarum RS20D has demonstrated the ability to remove both DBP and MBP in vitro, suggesting its potential as a detoxifying agent against these compounds. This study aimed to investigate the protective effects of RS20D on DBP or MBP-induced male reproductive toxicity in adolescent rats. Oral administration of RS20D significantly mitigated the histological damage to the testes caused by MBP or DBP, restored sperm concentration, morphological abnormalities, and the proliferation index in MBP-exposed rats, and partially reversed spermatogenic damage in DBP-exposed rats. Furthermore, RS20D restored serum levels of estradiol (E2) and testosterone, and superoxide dismutase (SOD) activity in DBP-exposed rats, significantly increased testosterone levels in MBP-exposed rats, and restored copper (Cu) concentrations in the testes after exposure to DBP or MBP. Additionally, RS20D effectively modulated the intestinal microbiota in DBP-exposed rats and partially ameliorated dysbiosis induced by MBP, which may be associated with the alleviation of reproductive toxic effects induced by DBP or MBP. In conclusion, this study demonstrates that RS20D administration can alleviate male reproductive toxicity and gut dysbacteriosis induced by DBP or MBP exposure, providing a dietary strategy for the bioremediation of PAEs and their metabolites.
研究领域:
毒理学
·
生殖生物学
·
微生物学
·
营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2020
·
IF 4.099
Xi Zhao,Zhenhua Liu,Jie Gao,Hu Li,Xiaorong Wang,Yinchuan Li,Fei Sun
Busulfan is commonly used for cancer chemotherapy, nevertheless it cause male infertility via damaging the germ cells. Therefore, the underlying mechanism should be explored. In the present study, we demonstrated for the first time that ferroptosis was involved in busulfan-induced oligospermia in mice. Mice were given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight to establish the model of oligospermia. Four weeks later, the results showed that busulfan-treated mice exhibited decreased sperm concentration and motility, along with features of typical ferroptosis in testis, such as increased malondialdehyde (MDA) content and prostaglandin-endoperoxide synthase (PTGS2) mRNA expression, and decreased NADPH content. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially alleviated busulfan-induced oligospermia in mice. Additionally, we also revealed that busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Fer-1 or DFO obviously reversed busulfan-induced ferroptosis by increasing Nrf2, GPX4 and FPN1 expressions. Furthermore, after activation of Nrf2 by sulforaphane, sperm concentration and motility in busulfan-treated mice increased, accompanied by enhanced expressions of GPX4 and FPN1. These findings imply that busulfan-induced ferroptosis might be mediated via inhibition of Nrf2-GPX4 (FPN1) signaling pathway, and highlight that targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility.
研究领域:
药理学
·
生殖生物学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Jinyuan Hu,Xu Luo,Mogellah John Panga,Clara Appiah,Vladimir Retyunskiy,Lin Zhu,Ye Zhao
Zinc pyrithione (ZPT) is widely recognized for its beneficial properties as an antifouling, antibacterial, and antifungal agent. Despite its positive industrial contributions, ZPT has been proven to exhibit toxicity towards various ecosystems, particularly affecting marine life. However, there is still a dearth of comprehensive research on ZPT toxicity and its toxicological mechanism in reproductive systems of aquatic organisms. In our study, we conducted a thorough analysis and unveiled a multitude of abnormalities in zebrafish sperm and testicular tissue caused by ZPT exposure, including a dose-dependent diminishing of testosterone levels, various sperm deformities, decreased sperm concentration and motility, and ROS-induced testicular tissue DNA damage. In addition, our study suggested that ZPT-induced testicular damage is associated with heightened oxidative stress, apoptosis, and possible hyperpolarization of the mitochondrial membrane. Through RNA-seq analysis, a total of 409 DEGs associated with ZPT-induced testicular injury were identified, and the hub gene was determined using a protein-protein interaction network (PPI). The genes and pathways uncovered in this study point to potential mechanisms of ZPT exposure on sperm and testicular injury in zebrafish.
研究领域:
环境毒理学
·
生殖生物学
·
水生毒理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）