Tesarik Jan, Mendoza Tesarik Raquel
MARGen (Molecular Assisted Reproductiona and Genetics) Clinic, 18006 Granada, Spain.
Int J Mol Sci. 2025 Jun 27;26(13):6217. doi: 10.3390/ijms26136217.
In addition to the male genome, the fertilizing spermatozoon delivers to the oocyte several factors whose deficiency can cause embryo dysfunction. Sperm oocyte-activating factor, identified as phoshoplipase C zeta (PLCζ), drives oocyte exit from meiotic arrest through a signaling pathway initiated by periodic rises of free cytosolic Ca concentration (calcium oscillations). Sperm centrioles, together with oocyte proteins, form centrosomes that are responsible for aster formation, pronuclear migration, and DNA polarization before nuclear syngamy and subsequent mitotic divisions. Sperm DNA fragmentation can be at the origin of aneuploidies, while epigenetic issues, mainly abnormal methylation of DNA-associated histones, cause asynchronies of zygotic gene activation among embryonic cells. Sperm long and short non-coding RNAs are important epigenetic regulators affecting critical developmental processes. Dysfunction of sperm PLCζ, centrioles, DNA, and RNA mostly converge to aneuploidy, developmental arrest, implantation failure, miscarriage, abortion, or offspring disease. With the exception of DNA fragmentation, the other sperm issues are more difficult to diagnose. Specific tests, including heterologous human intracytoplasmic sperm injection (ICSI) into animal oocytes, genetic testing for mutations in (the gene coding for PLCζ in humans) and associated genes, and next-generation sequencing of sperm transcriptome, are currently available. Oral antioxidant treatment and in vitro selection of healthy spermatozoa can be used in cases of sperm DNA fragmentation, while ICSI with assisted oocyte activation is useful to overcome oocyte-activation defects. No clinically confirmed therapy is yet available for sperm RNA issues.
除了雄性基因组外，受精精子还向卵母细胞传递多种因子，这些因子的缺乏会导致胚胎功能障碍。精子卵母细胞激活因子，即磷脂酶Cζ（PLCζ），通过由游离胞质钙浓度周期性升高引发的信号通路（钙振荡）驱动卵母细胞从减数分裂阻滞中退出。精子中心粒与卵母细胞蛋白一起形成中心体，负责在核融合及随后的有丝分裂之前形成星体、原核迁移和DNA极化。精子DNA片段化可能是非整倍体的起源，而表观遗传问题，主要是与DNA相关组蛋白的异常甲基化，会导致胚胎细胞间合子基因激活的不同步。精子长链和短链非编码RNA是影响关键发育过程的重要表观遗传调节因子。精子PLCζ、中心粒、DNA和RNA的功能障碍大多会导致非整倍体、发育停滞、着床失败、流产、堕胎或后代疾病。除了DNA片段化外，其他精子问题更难诊断。目前有一些特定的检测方法，包括将异源人类胞浆内单精子注射（ICSI）到动物卵母细胞中、对PLCζ（人类中编码PLCζ的基因）及相关基因的突变进行基因检测，以及对精子转录组进行下一代测序。对于精子DNA片段化的情况，可以采用口服抗氧化剂治疗和体外选择健康精子，而ICSI结合辅助卵母细胞激活有助于克服卵母细胞激活缺陷。目前尚无针对精子RNA问题的临床确诊治疗方法。
