Bleomycin in vitro exposure decreases markers of human male gamete competence.

Ana Lobo de Almeida, Ana Gonçalves, Alberto Barros, Mário Sousa, Rosália Sá
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Abstract

Objective: To investigate the in vitro impact of bleomycin on human sperm deoxyribonucleic acid (DNA) integrity, functionality, and morphology, with the aim of elucidating the underlying mechanism and anticipating potential repercussions on patients' reproductive function.

Design: Controlled laboratory-based in vitro investigation.

Setting: University and clinical in vitro fertilization treatment center.

Patient(s): Surplus human ejaculate donated for research by 45 reproductive-age participants exhibiting normozoospermic sperm parameters after clinical semen analysis. None of the participants had received a cancer diagnosis or undergone radiotherapy, chemotherapy, or both.

Intervention(s): After clinical semen analysis, sperm samples were centrifuged, diluted in sperm preparation medium, and exposed to bleomycin (100 μg/mL) for 2 hours at 37 °C in a humidified incubator with 5% CO2.

Main outcome measure(s): In vitro human sperm competence was evaluated by comparing raw sperm, sperm incubated with sperm preparation medium, and sperm exposed to bleomycin. Competence indicators included sperm motility, vitality, DNA and acrosome integrity, and mitochondrial membrane potential. Transmisson electron microscopy was employed to correlate the ultrastructural morphological findings with functional assays.

Result(s): Exposure to bleomycin for 2 hours in vitro significantly decreased sperm vitality, motility, and chromatin condensation compared with raw and control sperm. It also significantly increased sperm DNA fragmentation and the proportion of sperm with low mitochondrial membrane potential. Additionally, bleomycin significantly retarded the acrosomal response compared with control but did not affect the formation of intracellular and extracellular reactive oxygen species. Bleomycin-induced ultrastructural morphological changes supported the detected functional alterations.

Conclusion(s): Bleomycin negatively impacts male gamete competency in humans. Healthcare professionals should vigilantly monitor and further investigate the gonadotoxicity effects of bleomycin, in addition to its recognized lung toxicity. Meanwhile, it is recommended that patients with cancer undergoing bleomycin-containing chemotherapy regimens receive guidance on fertility preservation strategies.

博莱霉素体外暴露会降低人类男性配子能力的标志物。
目的:研究博莱霉素对人类精子DNA完整性、功能和形态的体外影响:研究博莱霉素对人类精子DNA完整性、功能和形态的体外影响,旨在阐明其潜在机制并预测对患者生殖功能的潜在影响:设计:实验室体外对照研究:45名育龄参与者捐献的多余人类射精用于研究,这些参与者在临床精液分析后显示出正常无精症精子参数。所有参与者均未接受过癌症诊断,也未接受过放疗、化疗或同时接受这两种治疗:临床精液分析后,对精子样本进行离心,在精子制备培养基(SPM)中稀释,并在37ºC、5% CO2的加湿培养箱中接触博莱霉素(100 μg/mL)两小时:主要结果指标:通过比较原始精子、经 SPM 培养的精子和暴露于博莱霉素的精子,对体外人类精子能力进行评估。能力指标包括精子运动能力、活力、DNA和顶体完整性以及线粒体膜电位。透射电子显微镜将超微结构形态学结果与功能测定结果联系起来:结果:与未处理精子和对照精子相比,体外暴露于博莱霉素两小时会显著降低精子活力、运动能力和染色质凝集(P < 0.001)。博莱霉素还能明显(P < 0.001)增加精子的DNA碎片和线粒体膜电位低的精子比例。此外,与对照组相比,博莱霉素明显(P < 0.05)延缓了顶体反应,但不影响细胞内和细胞外活性氧的形成。博莱霉素诱导的超微结构形态学变化支持了检测到的功能性改变:博莱霉素对人类男性配子能力有负面影响。结论:博莱霉素对人类男性配子能力有负面影响,医护人员应警惕并进一步研究博莱霉素的性腺毒性影响。同时,建议接受博莱霉素化疗方案的癌症患者接受生育力保护策略指导。
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
F&S science
F&S science Endocrinology, Diabetes and Metabolism, Obstetrics, Gynecology and Women's Health, Urology
CiteScore
2.00
自引率
0.00%
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0
审稿时长
51 days
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