ACTL7A,也称为Actin-like 7A,是一种重要的基因,编码一种类似于肌动蛋白的蛋白质。这种蛋白质在精子的形成和功能中发挥关键作用,尤其是在精子顶体(acrosome)的形成和功能方面。顶体是精子头部的一个结构,含有多种酶,对于精子和卵子的结合至关重要。ACTL7A通过与其他蛋白质相互作用,形成复杂的亚顶体区域,参与顶体的形成和维持其与核膜的连接[1,2,3,4,5,6,7,8,9,10]。
研究发现,ACTL7A基因的突变与男性不育和受精失败密切相关。例如,在人类中,ACTL7A基因的突变导致精子顶体异常,进而导致精子与卵子的结合失败,最终导致不育[3,5,7]。此外,ACTL7A基因的突变还可能导致精子头部形状异常,如小头精子,这也会影响精子的受精能力[6]。
在动物模型中,Actl7a基因的敲除(knockout)导致小鼠精子顶体形成异常,精子头部变形,以及受精失败[2,4]。这些发现表明,ACTL7A基因在精子的形成和功能中发挥着至关重要的作用。
除了顶体形成,ACTL7A基因还可能参与其他精子形成过程,如精子细胞质滴的形成和精子运动[4]。研究发现,Actl7a基因敲除小鼠的精子细胞质滴形成异常,精子运动能力下降。这表明,ACTL7A基因可能在精子细胞质滴的形成和精子运动中发挥作用。
此外,ACTL7A基因还可能参与早期胚胎发育过程。研究发现,ACTL7A基因的突变导致小鼠胚胎发育异常,甚至死亡[6]。这表明,ACTL7A基因可能在早期胚胎发育中发挥作用。
综上所述,ACTL7A基因在精子的形成和功能中发挥着至关重要的作用,其突变可能导致男性不育和受精失败。此外,ACTL7A基因还可能参与早期胚胎发育过程。因此,研究ACTL7A基因的功能和突变机制对于理解男性不育和受精失败的发生机制具有重要意义,并为开发新的治疗方法提供理论基础。
参考文献:
1. Xue, Yamei, Cheng, Xiaohong, Xiong, Yuping, Li, Kun. 2022. Gene mutations associated with fertilization failure after in vitro fertilization/intracytoplasmic sperm injection. In Frontiers in endocrinology, 13, 1086883. doi:10.3389/fendo.2022.1086883. https://pubmed.ncbi.nlm.nih.gov/36589837/
2. Wei, Yiqiu, Wang, Jingxuan, Qu, Rui, Li, Lin, Yin, Tailang. . Genetic mechanisms of fertilization failure and early embryonic arrest: a comprehensive review. In Human reproduction update, 30, 48-80. doi:10.1093/humupd/dmad026. https://pubmed.ncbi.nlm.nih.gov/37758324/
3. Wang, Meng, Zhou, Juepu, Long, Rui, Zhu, Lixia, Jin, Lei. 2023. Novel ACTL7A variants in males lead to fertilization failure and male infertility. In Andrology, , . doi:10.1111/andr.13553. https://pubmed.ncbi.nlm.nih.gov/37991128/
4. Zhou, Xiaopei, Liu, Zhenxing, Jia, Weimin, Hou, Meiqi, Zhang, Xianqin. 2022. Actl7a deficiency in mice leads to male infertility and fertilization failure. In Biochemical and biophysical research communications, 623, 154-161. doi:10.1016/j.bbrc.2022.07.065. https://pubmed.ncbi.nlm.nih.gov/35921706/
5. Zhou, Xiaopei, Xi, Qingsong, Jia, Weimin, Jin, Lei, Zhang, Xianqin. 2022. A novel homozygous mutation in ACTL7A leads to male infertility. In Molecular genetics and genomics : MGG, 298, 353-360. doi:10.1007/s00438-022-01985-0. https://pubmed.ncbi.nlm.nih.gov/36574082/
6. Zhang, Yini, Tang, Jianan, Wang, Xuemei, Sun, Xiaoxi, Xin, Aijie. 2023. Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex. In Reproductive biology and endocrinology : RB&E, 21, 82. doi:10.1186/s12958-023-01130-5. https://pubmed.ncbi.nlm.nih.gov/37667331/
7. Dai, Jing, Chen, Yongzhe, Li, Qi, Zheng, Wei, Lin, Ge. . Pathogenic variant in ACTL7A causes severe teratozoospermia characterized by bubble-shaped acrosomes and male infertility. In Molecular human reproduction, 28, . doi:10.1093/molehr/gaac028. https://pubmed.ncbi.nlm.nih.gov/35863052/
8. Zhang, Qi, Jin, Huijuan, Long, Shunhua, Chen, Suren, Lin, Tingting. . Deletion of ACTRT1 is associated with male infertility as sperm acrosomal ultrastructural defects and fertilization failure in human. In Human reproduction (Oxford, England), 39, 880-891. doi:10.1093/humrep/deae031. https://pubmed.ncbi.nlm.nih.gov/38414365/
9. Zhao, Shuai, Cui, Ying, Guo, Shunli, Chen, Zijiang, Zhao, Han. 2023. Novel variants in ACTL7A and PLCZ1 are associated with male infertility and total fertilization failure. In Clinical genetics, 103, 603-608. doi:10.1111/cge.14293. https://pubmed.ncbi.nlm.nih.gov/36593593/
10. Arora, Manvi, Mehta, Poonam, Sethi, Shruti, Samara, Mary, Singh, Rajender. 2024. Genetic etiological spectrum of sperm morphological abnormalities. In Journal of assisted reproduction and genetics, 41, 2877-2929. doi:10.1007/s10815-024-03274-8. https://pubmed.ncbi.nlm.nih.gov/39417902/