THC和精子:对受精能力的影响,体外植入前的发育和表观遗传修饰
Alexander G Kuzma-Hunt1, Reem Sabry1, Ola S Davis1
1Reproductive Health and Biotechnology Lab, Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
PloS one
|March 27, 2024
概括
全球大麻使用量正在上升,但其对男性生育能力的影响尚不清楚. 这项研究表明,精子中的Delta-9-tetrahydrocannabinol (THC) 暴露会对体外受精 (IVF) 后的胚胎发育产生负面影响,影响精子功能和表观遗传因素.
科学领域:
- 生殖生物学 生殖生物学
- 内分泌学 在内分泌学.
- 毒理学 毒理学 毒理学
背景情况:
- 全球大麻使用量大幅增加,大量使用者是生殖年龄的男性.
- 大麻中主要的精神活性化合物德尔塔-9-四大麻 (THC) 干扰了调节男性生殖功能的内分泌系统 (ECS).
- 以前的研究表明,THC会影响精子电容和基因表达,但它对精子功能和辅助生殖技术 (ARTs) 的影响仍然没有确定性.
研究的目的:
- 为了研究体外THC暴露对精子形态功能和内在特征的影响.
- 评估THC暴露精子在体外受精 (IVF) 后对胚胎发育的影响.
- 分析THC治疗后精子和由此产生的胚胎中与生育相关的microRNAs (miRs) 的变化.
主要方法:
- 牛精子是人类精子的转化模型,在体外暴露于THC的不同度 (0.032μM,0.32μM,4.8μM),模拟治疗和娱乐用途.
- 在6小时的THC治疗后,评估了精子功能参数,包括体反应和线粒体膜潜力 (MMP).
- 试管婴儿使用THC处理的精子进行了试管婴儿,随后评估了胚胎发育,重点关注囊胚细胞数量 (热囊细胞和内细胞质量) 和与生育相关的miR水平.
主要成果:
- 暴露于THC并没有影响体反应,但最高度 (4.8μM) 显著降低了MMP,这表明一种涉及CB受体激动机制.
- 虽然受精率没有受到影响,但用0.32-4.8μMTHC治疗的精子衍生出的胚胎囊显示了热囊细胞数量的减少,所有THC度都导致内细胞质细胞减少,特别是在0.032μM.
- 特定的与生育相关的miRs (miR-346,miR-324,miR-33b,miR-34c) 在暴露于THC的精子和由此产生的胚芽细胞中呈现出改变的水平,表明潜在的表观遗传修饰.
结论:
- 在体外暴露于THC可能会对精子中的关键形态功能和表观遗传因素产生负面影响,这些因素对受精和胚胎发育至关重要.
- 这项研究提供了第一个证据,表明THC诱导的精子变化可以在试管婴儿后损害胚胎质量.
- 这些发现强调了父亲使用大麻对生殖结果的潜在风险,以及需要进一步的临床研究.
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