Gat Itai, Orvieto Raoul
IVF Unit, Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Basic Clin Androl. 2017 May 21;27:9. doi: 10.1186/s12610-017-0054-y. eCollection 2017.
Mammalian reproduction is one of the most complex and fascinating biological phenomenon, which aims to transfer maternal and paternal genetic material to the next generation. At the end of oogenesis and spermatogenesis, both haploid gametes contain a single set of chromosomes ready to form the zygote, the first cell of the newly developing individual. The mature oocyte and spermatozoa remain in a quiescent state, during which the oocyte is characterized by nuclear and cytoplasmic arrest, while the spermatozoa necessitates further maturation within the epididymis and female reproductive track prior to egg fertilization. Either in vivo or in vitro, the sperm initiates a series of irreversible biochemical and physiological modifications in the oocyte. The earliest detected signal after fertilization is cytosolic Ca oscillations, a prerequisite step for embryo development. These oscillations trigger the release of the oocyte from the second meiosis arrest towards embryogenesis, also known as "oocyte activation". Phospholipase C zeta (PLCζ) is a unique sperm-soluble protein responsible for triggering the InsP/Ca pathway within the oocyte, leading to Ca oscillations and consequently to embryo development. The specific structure of PLCζ (compared to other PLCs) enables its specialized activity via the preserved X and Y catalytic domains, as well as distinct features such as rapid onset, high sensitivity to Ca and cession of oscillations upon zygote formation. The emerging discoveries of PLCζ have stimulated studies focusing on the possible clinical applications of this protein in male infertility evaluation and management during IVF/ICSI. Fertilization failure is attributed to lack of oocyte second meiosis resumption, suggesting that ICSI failure may be related to impaired PLCζ activity. Microinjection of recombinant human PLCζ to human oocytes after ICSI fertilization failure may trigger Ca oscillations and achieve successful fertilization, offering new hope for couples traditionally referred to sperm donation. However, more studies are still required prior to the routine implementation of this approach in the clinic. Directions for future studies are discussed.
哺乳动物的繁殖是最复杂且迷人的生物学现象之一，其目的是将母本和父本的遗传物质传递给下一代。在卵子发生和精子发生结束时，两个单倍体配子都包含一套准备好形成受精卵的染色体，受精卵是新发育个体的第一个细胞。成熟的卵母细胞和精子处于静止状态，在此期间，卵母细胞的特征是核和细胞质停滞，而精子在附睾和雌性生殖道中需要进一步成熟才能使卵子受精。无论是在体内还是体外，精子都会在卵母细胞中引发一系列不可逆的生化和生理变化。受精后最早检测到的信号是胞质钙振荡，这是胚胎发育的一个先决步骤。这些振荡触发卵母细胞从第二次减数分裂停滞中释放出来进入胚胎发生，也称为“卵母细胞激活”。磷脂酶Cζ（PLCζ）是一种独特的精子可溶性蛋白，负责触发卵母细胞内的肌醇磷酸/钙途径，导致钙振荡并进而导致胚胎发育。PLCζ的特定结构（与其他PLC相比）通过保留的X和Y催化结构域实现其特殊活性，以及诸如快速起效、对钙的高敏感性和受精卵形成时振荡停止等独特特征。PLCζ的新发现激发了对该蛋白在体外受精/卵胞浆内单精子注射（IVF/ICSI）期间男性不育评估和管理中的可能临床应用的研究。受精失败归因于卵母细胞第二次减数分裂恢复的缺乏，这表明ICSI失败可能与PLCζ活性受损有关。在ICSI受精失败后将重组人PLCζ显微注射到人类卵母细胞中可能会触发钙振荡并实现成功受精，为传统上依赖精子捐赠的夫妇带来了新希望。然而，在临床上常规实施这种方法之前，仍需要更多的研究。本文讨论了未来研究的方向。
