Research question

Treatments for Hodgkin lymphoma have improved but one of their common effects is gonadal toxicity, which contributes to fertility damage of patients and induces temporary or irreversible loss of fertility. Could micro-RNA (miRNA) expression profiles in follicular fluid be influenced by Hodgkin lymphoma? Could their alteration affect molecular pathways involved in follicle growth and oocyte maturation?

Design

miRNA expression profile was investigated in follicular fluid samples from young women affected by Hodgkin lymphoma compared with healthy controls by NanoString technology. Bioinformatic analysis was used to verify miRNA involvement in follicle development and miRNA deregulation with Hodgkin lymphoma in a larger cohort of follicular fluid samples was confirmed by real-time quantitative polymerase chain reaction.

Results

Thirteen miRNAs are deregulated in Hodgkin lymphoma samples compared with controls and are involved in molecular pathways related to cancer, gametogenesis and embryogenesis. Among them, let-7b-5p, miR-423-5p, miR-503-5p, miR-574-5p and miR-1303 are implicated in biological processes related to follicle development and oocyte maturation. Let-7b-5p holds the central position in the regulatory network of miRNA–mRNA interactions, has the highest number of mRNA target genes shared with the other differentially expressed miRNAs and is significantly downregulated in Hodgkin lymphoma follicular fluid samples.

Conclusions

These data led us to question the potential influence of miRNA deregulation on oocyte quality. Further studies are needed to verify the reproductive potential of young patients with Hodgkin lymphoma before starting chemotherapy protocols and an adequate protocol of fertility preservation needs to be guaranteed.

中文翻译：

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受霍奇金淋巴瘤影响的年轻女性卵泡液 microRNA 的分子分析

研究问题

霍奇金淋巴瘤的治疗有所改善，但其常见影响之一是性腺毒性，这会导致患者的生育能力受损并导致暂时或不可逆转的生育能力丧失。霍奇金淋巴瘤会影响卵泡液中的 micro-RNA (miRNA) 表达谱吗？它们的改变会影响参与卵泡生长和卵母细胞成熟的分子途径吗？

设计

通过 NanoString 技术，研究了来自受霍奇金淋巴瘤影响的年轻女性的卵泡液样本与健康对照的 miRNA 表达谱。生物信息学分析用于验证 miRNA 参与卵泡发育，并且通过实时定量聚合酶链反应证实了更大的卵泡液样本队列中霍奇金淋巴瘤的 miRNA 失调。

结果

与对照相比，霍奇金淋巴瘤样本中的 13 种 miRNA 失调，并参与与癌症、配子发生和胚胎发生相关的分子途径。其中，let-7b-5p、miR-423-5p、miR-503-5p、miR-574-5p和miR-1303与卵泡发育和卵母细胞成熟相关的生物学过程有关。Let-7b-5p 在 miRNA-mRNA 相互作用的调控网络中处于中心位置，与其他差异表达的 miRNA 共享的 mRNA 靶基因数量最多，并且在霍奇金淋巴瘤滤泡液样本中显着下调。

结论

这些数据使我们质疑 miRNA 失调对卵母细胞质量的潜在影响。在开始化疗方案之前，需要进一步的研究来验证年轻霍奇金淋巴瘤患者的生殖潜力，并且需要保证适当的生育力保存方案。