RESUMEN
Fertilization is a key process in biology to the extent that a new individual will be born from the fusion of two cells, one of which leaves the organism in which it was produced to exert its function within a different organism. The structure and function of gametes, and main aspects of fertilization are well known. However, we have limited knowledge about the specific molecules participating in each of the steps of the fertilization process due to the transient nature of gamete interaction. Moreover, if we specifically focus in the fusion of both gametes' membrane, we might say our molecular knowledge is practically null, despite that molecular mechanisms of cell-to-cell adhesion are well studied in somatic cells. Moreover, between both gametes, the molecular knowledge in the egg is even scarcer than in the spermatozoon for different reasons addressed in this review. Sperm-specific protein IZUMO1 and its oocyte partner, JUNO, are the first cell surface receptor pair essential for sperm-egg plasma membrane binding. Recently, thanks to gene editing tools and the development and validation of in vitro models, new oocyte molecules are being suggested in gamete fusion such as phosphatidylserine recognition receptors. Undoubtedly, we are in a new era for widening our comprehension on molecular fertilization. In this work, we comprehensively address the proposed molecules involved in gamete binding and fusion, from the oocyte perspective, and the new methods that are providing a better understanding of these crucial molecules.
RESUMEN
The fusion of gamete membranes during fertilization is an essential process for sexual reproduction. Despite its importance, only three proteins are known to be indispensable for sperm-egg membrane fusion: the sperm proteins IZUMO1 and SPACA6, and the egg protein JUNO. Here we demonstrate that another sperm protein, TMEM95, is necessary for sperm-egg interaction. TMEM95 ablation in mice caused complete male-specific infertility. Sperm lacking this protein were morphologically normal exhibited normal motility, and could penetrate the zona pellucida and bind to the oolemma. However, once bound to the oolemma, TMEM95-deficient sperm were unable to fuse with the egg membrane or penetrate into the ooplasm, and fertilization could only be achieved by mechanical injection of one sperm into the ooplasm, thereby bypassing membrane fusion. These data demonstrate that TMEM95 is essential for mammalian fertilization.