Selenium mitigates methotrexate-induced testicular injury: Insights from male NMRI mice model

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY Birth Defects Research Pub Date : 2024-02-13 DOI:10.1002/bdr2.2315

Mohammadreza Gholami, Afsaneh Nemati, Azita Alasvand Zarasvand, Abolfazl Zendehdel, Cyrus Jalili, Iraj Rashidi, Kamran Mansouri, Forough Taheri, Vahideh Assadollahi, Elham Gholami

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Abstract

Background and Aim

Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury.

Materials and Methods

Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05).

Results

Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties.

Conclusion

Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility.

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硒可减轻甲氨蝶呤引起的睾丸损伤：雄性 NMRI 小鼠模型的启示。

背景和目的：化疗，尤其是甲氨蝶呤（MTX），经常引起睾丸毒性，导致精子发生障碍和激素失衡。本研究旨在探讨硒（Se）对 MTX 引起的睾丸损伤的潜在保护作用：雄性小鼠分为对照组、MTX 组、Se 组和 MTX + Se 组。组织病理学检查包括使用约翰森小管活检评分法（JTBS）制备睾丸组织切片，以评估精子发生情况。生化检验包括评估睾酮、丙二醛（MDA）、黄体生成素（LH）和促卵泡激素（FSH）水平。采用实时定量聚合酶链反应（RT-qPCR）分析了caspase 3（casp3）、肿瘤蛋白53（p53）、B细胞淋巴瘤2（Bcl2）和Bcl2相关X蛋白（Bax）基因的表达。统计分析采用方差分析和 Tukey 检验（P 结果）：组织病理学分析表明，MTX 组睾丸明显受损，精子发生和雷迪格细胞数量减少，而 Se 组则减轻了这些影响，保持了生殖上皮细胞结构的完整性。生化分析表明，MTX导致丙二醛（MDA）水平升高，睾酮、LH和FSH水平降低，表明存在氧化应激和Leydig细胞功能障碍。基因表达分析表明，MTX 上调了促凋亡基因（casp3、p53 和 bax），同时下调了抗凋亡基因 Bcl2。与此相反，Se 治疗逆转了这些趋势，凸显了其潜在的抗凋亡特性：我们的研究结果强调了Se作为一种治疗剂，减轻MTX诱导的睾丸损伤相关生殖毒性的潜力。Se 可通过调节氧化应激、保持激素平衡和调节细胞凋亡途径发挥保护作用。这些结果表明，补充Se可能是减轻化疗引起的睾丸损伤和保护男性生育能力的一种有前途的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.