Biomedicines
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2024
·Vol. 12
·期 8
·1632
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IF 3.9
Hang Zhang,Nannan Li,Yukun Zhang,Yue Xu,Feng Lu,Dongmei Lin,Shuqian Lin,Min Li,Baoxue Yang
Chemotherapy is an important factor leading to male infertility. It is crucial to discover safe and effective treatments to prevent male reproductive injury caused by chemotherapy. TheGanoderma lucidumpolysaccharide peptide (GLPP) has multiple pharmacological activities. The purpose of this study was to determine whether GLPP could protect the male sperm production from chemotherapeutic injury using a mouse model, with testicular damage induced by cyclophosphamide (CP). CP (50 mg/kg/day) was injected intraperitoneally into male ICR mice gavaged with different doses of GLPP at certain spermatogenic stages. The experimental results showed that GLPP alleviated the CP-induced reduction in reproductive organ coefficients and sperm parameters and reduced the morphological damage of testicular tissues in a dose-dependent manner. GLPP significantly improved the reproductive index, sperm-related parameters, sex hormone levels, and histological testis architecture at different spermatogenic stages. Furthermore, GLPP significantly increased superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), Nrf2, and HO-1, and decreased malondialdehyde (MDA) and Keap-1 in the testicular tissue, indicating reduced oxidative stress. In addition, GLPP limited CP-induced apoptosis via a reduction in Bax expression and increase in Bcl-2 expression. This study suggests that GLPP plays a protective role in spermatogenesis by reducing chemotherapeutic injury and might be developed into drug for male patients receiving chemotherapy.
研究领域:
药理学
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生殖生物学
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肿瘤学
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DOI
PubMed
高影响因子
Food & Function
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2024
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IF 5.1
Jingyi Ren,Jiarui Liu,Jinshi Zuo,Zhenao Zhang,Dan Huang,Xuanyi Liu,Miaomiao Lu,Yadong Zhang,Yang Su,Yuxia Ma
Background: Perfluorooctane sulfonate (PFOS) is a persistent, widely present environmental pollutant, and its toxicity to male reproduction has gradually attracted attention. Flaxseed oil (FO) is a dietary oil abundant in α-linolenic acid and has been demonstrated to possess multiple health benefits. However, whether FO protects against PFOS-induced testicular injury and its mechanism remain unclear. Methods: C57/BL6 mice were gavaged with different concentrations of FO or PFOS (10 mg kg−1) for 28 days. Blood and testicular tissues were collected for histopathology, proteomics, and biochemical and molecular analyses. Results: Our results showed that FO supplementation significantly attenuated PFOS-induced testicular injury, as indicated by histopathological changes, decreased oxidative stress level, increased sperm count, decreased rate of sperm malformation, and improved functional markers of spermatogenesis. Proteomic analysis showed that differentially expressed proteins were notably enriched in spliceosome pathways. Machine learning algorithms were used to screen the hub gene, and PRPF3 and PUF60 proteins were found to be important for FO to exert protective benefits to testicular injury. Western blot results confirmed that FO supplementation could increase the protein expression of PRPF3 and decrease the protein expression of PUF60 in PFOS-exposed mice. Conclusions: This study revealed that FO can alleviate PFOS-induced testicular dysfunction by regulating RNA alternative splicing. The spliceosome-related proteins PRPF3 and PUF60 may be the potential targets for FO to alleviate PFOS-induced testicular injury. FO supplementation may be an effective dietary intervention to prevent adverse effects of PFOS on testes.
研究领域:
毒理学
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生殖生物学
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营养科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
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2024
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IF 4
Kun MA,Mengnan LI,Yahui SONG,Xinjing MAO,Shaolan ZHANG,Yaping ZHANG,Yuning JIANG,Chuanyuan JI,Kunxu NIU,Hongrong LI,Yunlong HOU,Cong WEI
Bazi Bushen (BZBS), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy in testicular dysfunction within D-galactose and NaNO 2 mouse models. This study aimed to ascertain if BZBS could also mitigate the decline in testicular function associated with natural aging. Therefore, male aged mice were employed to evaluate the preventive effects of BZBS on male reproductive aging. This was achieved by assessing sex hormone production, testicular histomorphology, and spermatogenesis. Relative to the untreated aged control group, BZBS administration elevated the levels of sex hormones and spermatocyte populations and preserved normal testicular structure in aged mice. Notably, spermatogenesis was maintained. Further analyses, including malondialdehyde (MDA) assays and real-time PCR, indicated that BZBS diminished testicular oxidative stress and the inflammatory burden. Corroborating these findings, mice treated with BZBS exhibited reductions in the populations of senescent and apoptotic cells within the seminiferous tubules, suggesting alleviated cellular damage. In contrast, we observed that rapamycin, a drug known for its longevity benefits, induced excessive testicular apoptosis and did not decrease lipid peroxidation. Collectively, our results highlight BZBS’s promising clinical potential in counteracting male reproductive aging, underlining its mechanisms of action.
研究领域:
中医
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生殖生物学
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衰老研究
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药理学
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Xu Huang,Yan Fu,Siyuan Wang,Qitong Guo,Yuhao Wu,Xiangqin Zheng,Junke Wang,Shengde Wu,Lianju Shen,Guanghui Wei
2,2′,4,4′-Tetrabromodiphenyl ether (PBDE-47), being the most prevalent congener of polybrominated diphenyl ethers (PBDEs), has been found to accumulate greatly in the environment and induce spermatogenesis dysfunction. However, the specific underlying factors and mechanisms have not been elucidated. Herein, male Sprague-Dawley (SD) rats were exposed to corn oil, 10 mg/kg body weight (bw) PBDE-47 or 20 mg/kg bw PBDE-47 by gavage for 30 days. PBDE-47 exposure led to blood-testis barrier (BTB) integrity disruption and aberrant spermatogenesis. Given that Sertoli cells are the main toxicant target, to explore the potential mechanism involved, we performed RNA sequencing (RNA-seq) in Sertoli cells, and the differentially expressed genes were shown to be enriched in ferroptosis and lysosomal pathways. We subsequently demonstrated that ferroptosis was obviously increased in testes and Sertoli cells upon exposure to PBDE-47, and the junctional function of Sertoli cells was restored after treatment with the ferroptosis inhibitor ferrostatin-1. Since glutathione peroxidase 4 (GPX4) was dramatically reduced in PBDE-47-exposed testes and Sertoli cells and considering the RNA-sequencing results, we examined the activity of chaperone-mediated autophagy (CMA) and verified that the expression of LAMP2a and HSC70 was upregulated significantly after PBDE-47 exposure. Notably, Lamp2a knockdown not only inhibited ferroptosis by suppressing GPX4 degradation but also restored the impaired junctional function induced by PBDE-47. These collective findings strongly indicate that PBDE-47 induces Sertoli cell ferroptosis through CMA-mediated GPX4 degradation, resulting in decreased BTB-associated protein expression and eventually leading to BTB integrity disruption and spermatogenesis dysfunction.
研究领域:
毒理学
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生殖生物学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Jiaqi Li,Dezhi Chen,Jialiang Suo,Jiaqi Li,Yimu Zhang,Yu Wang,Zhewen Deng,Qi Zhang,Bo Ma
Triptolide (TP) is a major bioactive compound derived from Tripterygium wilfordii Hook . F . (TwHF) known for its medicinal properties, but it also exhibits potential toxic effects. It has been demonstrated to induce severe male reproductive toxicity, yet the precise mechanism behind this remains unclear, which limits its broad clinical application. This study aimed to investigate the mechanisms underlying testicular damage and spermatogenesis dysfunction induced by TP in mice, using both mouse models and the spermatocyte-derived cell line GC-2spd. In the present study, it was found that TP displayed significant testicular microstructure damaged and spermatogenesis defects including lower concentration and abnormal morphology by promoting ROS formation, MDA production and restraining GSH level, glutathione peroxidase 4 (GPX4) expression in vivo . Furthermore, Ferrostatin-1 (FER-1), a ferroptosis inhibitor, was found to significantly reduce the accumulation of lipid peroxidation, alleviate testicular microstructural damage, and enhance spermatogenic function in mice. Besides, notably decreased cell viability, collapsed mitochondrial membrane potential, and elevated DNA damage were observed in vitro . The above-mentioned phenomenon could be reversed by pre-treatment of FER-1, indicating that ferroptosis participated in the TP-mediated spermatogenesis dysfunction. Mechanistically, TP could enhance GPX4 ubiquitin degradation via triggering K63-linked polyubiquitination of GPX4, thereby stimulating ferroptosis in spermatocytes. Functionally, GPX4 deletion intensified ferroptosis and exacerbated DNA damage in GC-2 cells, while GPX4 overexpression mitigated ferroptosis induced by TP. Overall, these findings for the first time indicated a vital role of ferroptosis in TP induced-testicular injury and spermatogenic dysfunction through promoting GPX4 K63-linked polyubiquitination, which hopefully offers a potential therapeutic avenue for TP-related male reproductive damage. In addition, this study also provides a theoretical foundation for the improved clinical application of TP or TwHF in the future.
研究领域:
药理学
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生殖生物学
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细胞生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2024
·
IF 7.6
Shouchun Xiao,Jingna Cui,Yue Cao,Yaru Zhang,Jiaxing Yang,Li Zheng,Fanrong Zhao,Xueke Liu,Zhiqiang Zhou,Donghui Liu,Peng Wang
Chemical-caused reproductive dysfunction has emerged as a global public health concern. This study investigated the adverse effects of the organophosphorus pesticide malathion on reproductive function in adolescent male mice at environmentally relevant concentrations. The results indicated that eight-week malathion exposure reduced testis weight, caused sex and thyroid hormone disorders, and induced testicular spermatogenic epithelium damage and oxidative stress. Testicular RNA sequencing indicated that malathion significantly affected testicular energy metabolism, hypoxia-inducible factor 1 (HIF-1) signaling, and steroid hormone biosynthesis pathways. Malathion significantly increased the gene and protein expression of HIF-1α by upregulating key genes in the mitogen-activated protein kinase (MAPK) pathway ( Map2k2 , Mapk3 , and Eif4e2 ) and the phosphatidylinositol 3-kinase (PI3K) pathway ( Pik3r2 and Akt1 ). Furthermore, malathion downregulated HIF-1α degradation-regulating genes while upregulating anaerobic metabolism and inflammation-related genes, thereby inhibiting normoxia and promoting hypoxia processes. Testicular hypoxia subsequently induced steroid hormone biosynthesis disorders and spermatogenesis dysfunction. Molecular docking verified that malathion interfered with HIF-1α and steroid hormone synthases (CYP11A1, CYP17A1 and CYP19A1) by forming hydrogen bonds and hydrophobic interactions with these proteins. This study presents the first evidence that malathion triggers spermatogenesis dysfunction in mice through activating the HIF-1/MAPK/PI3K pathway, providing a comprehensive understanding of the reproductive toxicity risks associated with organophosphorus pesticides.
研究领域:
毒理学
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生殖生物学
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
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