由具有Tdrd6变异的精子引起的变异性致死性基因表达扰乱了早期胚胎发育
Zhijie Hu1, Yuqi Zhang1, Renfei Cai1
1Department of Assisted Reproduction Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai China.
MedComm
|January 7, 2025
概括
新型TDRD6变种由于卵细胞激活缺陷导致男性不孕不育和胚胎停产. 人工卵细胞激活 (AOA) 和莫斯mRNA注射成功恢复了生育能力,并使人类和小鼠的活产成为可能.
科学领域:
- 生殖生物学 生殖生物学
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
背景情况:
- 与精子相关的男性不孕症和胚胎停产的机制尚不清楚.
- 早期胚胎停产可能源于精子因素,影响生殖成功.
- TDRD6基因变异与男性不孕症有关.
研究的目的:
- 研究新型TDRD6变异在男性不孕症和胚胎停产中的作用.
- 阐明由TDRD6变体引起的卵细胞激活缺陷 (OAD) 的机制.
- 评估人工卵细胞激活 (AOA) 作为治疗策略.
主要方法:
- 生成了Tdrd6敲进和敲出鼠标模型.
- 分析了精子参数,包括脂酶C zeta定位.
- 在患者和小鼠模型中评估卵细胞激活和胚胎发育.
- 使用AOA和Mos mRNA注射进行治疗干预.
主要成果:
- 变种TDRD6的小鼠表现出橄酸氨基和胚胎停止 (OAT) 和胚胎停止,反映了人类病例.
- 受影响个体和小鼠的精子显示异常的脂酶C zeta局部化和OAD.
- AOA成功地恢复了生育能力,导致人类和小鼠的怀孕和活产.
- 在OAD影响基因表达的2-pronuclear (2PN) 阶段,与莫斯在逮捕中发挥关键作用.
结论:
- 与TDRD6变种相关的与精子相关的OAD是男性不孕症和早期胚胎停产的原因.
- AOA是TDRD6相关的男性不孕症和胚胎停止的有效治疗方法.
- OAD影响2PN阶段的基因表达,而Mos mRNA可以减轻胚胎停产,提供新的治疗途径.
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