Rojas Japhet, Hinostroza Fernando, Vergara Sebastián, Pinto-Borguero Ingrid, Aguilera Felipe, Fuentes Ricardo, Carvacho Ingrid
Laboratorio Fisiología de la Reproducción, Departamento de Biología y Química, Facultad de Ciencias Básicas, Universidad Católica del Maule, Talca, Chile.
Escuela de Ingeniería en Biotecnología, Facultad de Ciencias Agrarias y Forestales, Universidad Católica del Maule, Talca, Chile.
Front Cell Dev Biol. 2021 Sep 3;9:704867. doi: 10.3389/fcell.2021.704867. eCollection 2021.
Fertilization by multiple sperm leads to lethal chromosomal number abnormalities, failed embryo development, and miscarriage. In some vertebrate and invertebrate eggs, the so-called cortical reaction contributes to their activation and prevents polyspermy during fertilization. This process involves biogenesis, redistribution, and subsequent accumulation of cortical granules (CGs) at the female gamete cortex during oogenesis. CGs are oocyte- and egg-specific secretory vesicles whose content is discharged during fertilization to block polyspermy. Here, we summarize the molecular mechanisms controlling critical aspects of CG biology prior to and after the gametes interaction. This allows to block polyspermy and provide protection to the developing embryo. We also examine how CGs form and are spatially redistributed during oogenesis. During egg activation, CG exocytosis (CGE) and content release are triggered by increases in intracellular calcium and relies on the function of maternally-loaded proteins. We also discuss how mutations in these factors impact CG dynamics, providing unprecedented models to investigate the genetic program executing fertilization. We further explore the phylogenetic distribution of maternal proteins and signaling pathways contributing to CGE and egg activation. We conclude that many important biological questions and genotype-phenotype relationships during fertilization remain unresolved, and therefore, novel molecular players of CG biology need to be discovered. Future functional and image-based studies are expected to elucidate the identity of genetic candidates and components of the molecular machinery involved in the egg activation. This, will open new therapeutic avenues for treating infertility in humans.
多个精子受精会导致致命的染色体数目异常、胚胎发育失败和流产。在一些脊椎动物和无脊椎动物的卵子中，所谓的皮质反应有助于卵子激活，并在受精过程中防止多精入卵。这个过程涉及皮质颗粒（CGs）在卵子发生过程中于雌配子皮质的生物发生、重新分布以及随后的积累。CGs是卵母细胞和卵子特有的分泌囊泡，其内容物在受精时释放以阻止多精入卵。在这里，我们总结了配子相互作用前后控制CG生物学关键方面的分子机制。这有助于阻止多精入卵并为发育中的胚胎提供保护。我们还研究了CGs在卵子发生过程中如何形成以及在空间上如何重新分布。在卵子激活过程中，CG胞吐作用（CGE）和内容物释放由细胞内钙的增加触发，并依赖于母源加载蛋白的功能。我们还讨论了这些因子的突变如何影响CG动态，提供了前所未有的模型来研究执行受精的遗传程序。我们进一步探索了有助于CGE和卵子激活的母源蛋白和信号通路的系统发育分布。我们得出结论，受精过程中许多重要的生物学问题和基因型 - 表型关系仍未解决，因此，需要发现CG生物学的新分子参与者。未来基于功能和图像的研究有望阐明参与卵子激活的遗传候选物和分子机制的组成部分的身份。这将为治疗人类不孕症开辟新的治疗途径。
