Fertilization and oocyte activation: overview, updates, and novel hypotheses from a molecular perspective

The multifaceted process of fertilization encompasses a precisely orchestrated cascade of molecular and morphological modifications of the participating male and female gametes. Fertilization culminates in the union of the maternal and paternal genomes and ultimately spark the development of a new individual. During the last decade, extensive new knowledge has been gained concerning the candidate cellular and molecular mechanisms that guide each step of the process from the sperm journey through the female reproductive tract to the gamete fusion and oocyte activation. In this review, we aim at summarizing the main molecular mechanisms of sperm and oocyte activation and fertilization from the moment sperm enters the female reproductive system up to zygote formation. Focusing on molecular determinants including but not limited to ligands, receptors, and signal transducers, we describe well established and novel molecular candidates that pave the way throughout this complex process and highlight the need for further investigation toward clinical application in assisted reproductive therapy.