DUGi

Molecular mechanisms involved in sperm-oocyte interaction and oocyte activation. Infertility associated with the dysfunction of these mechanisms

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@20532

Infertility currently affects between 10% and 15% of the population worldwide, and it is associated with both male and female reproductive system disorders and alterations. On the other hand, idiopathic infertility, which cannot be attributed to either male or female factors, affects approximately 25% of infertile couples during their reproductive age. In this context, this Dissertation is focused on understanding the molecular mechanisms involved in the interaction of the gametes. This knowledge could serve as a starting point to relate the deficiency of these mechanisms to infertility. Following this objective, a systematic review of the current literature was carried out extracted using PubMed. This systematic review was subjected to specific selection criteria and subsequent quality analysis in order to establish the inclusion/exclusion of articles. From the selected articles, the process of fertilization in mammals was studied. This process consists of a set of complex stages in which different proteins, borne by both the sperm and the oocyte, play essential roles that warrant gamete interaction. Thus, studying the function and participation of these proteins is essential to understand and treat idiopathic infertility. During sperm capacitation, which is an indispensable process to acquire the ability to fertilize the oocyte, several sperm proteins, especially PKA and others of the SNAREs family, play a key role. In addition, hydrolytic enzymes released upon the acrosomal reaction, such as acrosin, and sperm receptors for both progesterone and ZP proteins are essential to achieve the ZP penetration capability. Subsequently, the interaction and fusion of the gamete membranes takes place, an event in which the sperm-specific protein IZUMO1 and the oocyte-specific one JUNO are primarily involved. In this regard, it has been observed that deficiencies in both proteins make gamete fusion impossible, which is associated with severe infertility problems. Finally, after membrane fusion, a series of calcium oscillations in the cytosol are triggered allowing oocyte activation. In this process, which is necessary for the oocyte to complete the second meiotic division, the sperm-specific protein PLCζ plays a key role. However, it seems that this protein would not carry out this function alone, since other proteins such as PAWP could also be involved. In conclusion, it is necessary to increase the knowledge of sperm and oocyte proteins involved in the events that occur before, during and after fertilization in order to understand how dysfunctions in the different molecular mechanisms involved in these processes are related to infertility. In this regard, deficiencies and/or alterations in several proteins, especially PLCζ, IZUMO1 and JUNO, have been found to be a cause of infertility. Thus, these crucial proteins could be used as tools for the prevention and diagnosis of infertility associated with the different molecular processes described, as they could also serve as a starting point for the study of idiopathic infertility. Nevertheless, as research is still in its infancy, further studies involving animal models and human are much warranted. Related with this, it is worth mentioning that additional difficulties on human research exist due to the limited availability of oocyte for scientific investigation