PLOS Biology:冷冻20多年的睾丸组织仍可产生有活力的精子,为癌症患儿带来新希望

2022-05-12 甲遇庚 “生物世界”公众号

近几十年,癌症疗法的突飞猛进,使儿童癌症患者的存活率不断提高。但这些儿童癌症患者在成人后却不得不面对一些因癌症治疗产生的副作用,如生育能力下降,甚至不育。

癌症,泛指所有的恶性肿瘤。虽然现代医学技术已发展到前所未有的高度,但我们如今依然“谈癌色变”。因为,癌症发病率和死亡人数还在逐年上升;而治愈后的幸存者还在不得不面对各种治疗产生的副作用,就比如那些儿童癌症患者。

近几十年,癌症疗法的突飞猛进,使儿童癌症患者的存活率不断提高。但这些儿童癌症患者在成人后却不得不面对一些因癌症治疗产生的副作用,如生育能力下降,甚至不育。

一种潜在的治疗方法是收集、冷冻并重新植入含有干细胞的睾丸组织。最近,在猕猴模型研究中,这种方法显示精原干细胞在短期冷冻并重新植入后,精子可以重新产生并用于生育后代。然而,这对于年龄较小的儿童而言,冷冻后的干细胞能否保存10年或更长时间后再重新植入,还缺乏相关的数据。

近日,美国宾夕法尼亚大学的研究团队在 PLOS Biology 期刊上发表了题为:Reestablishment of spermatogenesis after more than 20 years of cryopreservation of rat spermatogonial stem cells reveals an important impact in differentiation capacity 的研究论文。

这项大鼠研究证实,冷冻保存的雄性睾丸组织可以在23年后重新植入,并具备继续制造精子的能力

这表明,在长期低温保存过程中,睾丸组织中的精原干细胞的生存能力不会完全丧失,这将有助于识别生存能力降低或丧失的关键因素,从而改善男童癌症治疗后的生殖选择。

长期以来,大鼠一直是哺乳动物精子发生的重要模型。雄性大鼠生殖细胞分化的组织学过程已被科学家们充分了解。精原干细胞(SSC)是终身产生精子的基础,因为它们既可以自我更新,也可以分化成所有类型的生殖细胞。当将干细胞移植到缺乏生殖细胞的受体睾丸时,它具有再生精子的潜力。因此在保存或修饰雄性生殖系方面具有治疗应用方面的价值。

对于生殖系统还未发育成熟的儿童期癌症患者而言,尤其需要这种方法。但是,在收集精原干细胞冷冻后十年或更长时间后重新植入可能是不可行的。这就提出了一个问题,即冷冻的精原干细胞到底能存活多久。

为了探索这个问题,研究人员解冻了在实验室中冷冻超过23年的大鼠精原干细胞(SSC),并将它们植入裸鼠体内。这些裸鼠缺乏免疫反应,所以不会排斥外来组织。

然后,研究人员将冷冻23年的SSC与仅冷冻1至4个月的和新鲜收集的SSC产生活精子的能力进行了比较,所有这些都来自一个维持了几十年的大鼠群体。

研究人员发现,与当天采集的干细胞一样,冷冻23年的精原干细胞能够在小鼠睾丸中定植,并产生成功生成精子所需的所有类型的细胞。

研究人员表示,这是伟大的第一步,显示了长期冷冻后的干细胞在植入受体组织后恢复活性的能力。

但不得不承认的是,与新鲜收集和从几个月采集的组织样本中提取的干细胞相比,这些冷冻23年的干细胞在产生健康精子方面的表现较差。虽然与其他样本相比,长期冷冻的精原干细胞具有类似的基因表达变化,但它们产生的伸长型精子细胞较少,而这些细胞可以继续形成游动的精子。

总之,这项研究表明,大鼠精原干细胞可以成功冷冻20年以上,并在移植到不育受体动物体内,可以再生出产生精子的能力。这可以为因癌症治疗丧失生育能力的男孩提供一种解决方案。

研究人员表示,上述发现具有几个重要意义。首先指出了原位测试精原干细胞活力的重要性,而不是依靠生化或细胞生物标志物来确定冷冻细胞的潜力。因为,这可能不能反映随着时间推移干细胞潜力的实际损失。其次,虽然目前没有可以扩展到人类精原干细胞以进行再植入的方案,但假设人类精原干细胞与大鼠相似,这些方案可能需要考虑生存能力的时间依赖性退化。最后,这项研究显示,在长期低温保存过程中,生存能力不会丧失,这将有助于识别生存能力降低或丧失的关键因素,从而改善男童癌症治疗后的生殖选择。

原始出处:

Eoin C. Whelan, Fan Yang, Mary R. Avarbock, et al. Reestablishment of spermatogenesis after more than 20 years of cryopreservation of rat spermatogonial stem cells reveals an important impact in differentiation capacity. PLOS Biology, https://doi.org/10.1371/journal.pbio.3001618.

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    2022-05-16 sunylz
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    2022-05-26 珙桐
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    2022-05-14 zhangph

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绿茶是世界上流行的饮料,且含有多酚类物质,其抗氧化活性可以改善精子参数及其生育能力。

一颗精子的100种死法!6个你必须知道的男「性」研究

每年的今天(10月28日),是男性健康日。男性健康日最早是由世界卫生组织提出,意在提高整个社会对男性健康的关注。

Science子刊: 避孕抗体来了!从不孕女性体内提取,安全性99.9%

长久以来,意外怀孕都是一个令人苦恼的问题,人们在避孕的道路上可谓做出了不懈的努力,研究出了各种避孕方法。近日,来自美国北卡罗莱纳大学教堂山分校的研究人员提出了一种全新的避孕思路——抗体捕获精子。

Science:微管蛋白糖基化异常,男性不育的又一个潜在原因!

微管是真核细胞骨架的关键组成部分。有人提出,是微管蛋白翻译后修饰的组合形成的“微管蛋白密码”使微管适应活细胞内的特定功能,但仍缺乏相关机制研究。

Clin Epigenetics :精子中的生物标记物可能与后代自闭症相关

自闭症(ASD)是发生在婴儿时期的一种特殊性精神障碍,又称婴儿孤独症。过去曾经认为,其病因可能与社会心理因素有关。然而,最近《BMC》发布的一项研究却颠覆了人们的认知。