2型糖尿病影响人类精子中的DNA甲基化
Lei Su1,2, Jonathan M Dreyfuss3, Rafael Ferraz Bannitz1
1Research Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Clinical epigenetics
|March 20, 2025
概括
2型糖尿病与男性的高精子DNA甲基化有关,即使与BMI相似. 这些表观遗传变化可能会影响后代的健康,但需要进一步的研究来确定治疗的可逆性.
科学领域:
- 生殖生物学 生殖生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 内分泌学 在内分泌学.
背景情况:
- 生殖系统障碍,包括阴性腺和降低生育能力,是糖尿病的未被认可的并发症.
- 虽然小鼠研究表明高血糖和肥胖会改变精子表观遗传学,但人类数据有限.
- 2型糖尿病 (T2D) 与影响各种身体系统的代谢失调有关.
研究的目的:
- 研究2型糖尿病和血糖控制对人类精子质量和DNA甲基化的影响.
- 为了比较患有2型糖尿病和没有2型糖尿病的男性之间的精子DNA甲基化模式.
- 探索血糖控制 (HbA1c) 与精子中差异性DNA甲基化之间的潜在联系.
主要方法:
- 一项前性队列研究,涉及40名男性 (18名患有T2D,6名患有糖尿病前期,16名对照),所有男性的BMI>25 kg/m2.
- 对生殖荷尔蒙,精子度和运动性的分析.
- 使用MethylationEPIC BeadChip进行精子DNA甲基化分析,在3个月后在参与者的子集中重复采样.
主要成果:
- 与对照组相比,患有T2D的男性表现出更高的卵泡刺激激素 (FSH),但与对照组相比,和精子质量相似.
- 在糖尿病和对照组中,精子DNA甲基化在3个月内保持稳定.
- 在T2D男性与对照者的655个CpG位点观察到差异甲基化,其中96.5%显示甲基化增加.
- 不同的甲基化基因与突触信号传递,actin,cAMP和G蛋白结合受体通路有关.
- 24%的不同调节的探头与与HbA1c相关的探头重叠.
结论:
- 与类似BMI的正常血糖男性相比,患有2型糖尿病的男性表现出高的精子DNA甲基化水平.
- 这些表观遗传变化的临床意义和潜在可逆性与降血糖治疗需要进一步调查.
- 这些发现突显了T2D对生殖健康和后代发育的潜在表观遗传贡献.
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