The molecular basis of fertilization (Review)

Abstract

Fertilization is the fusion of the male and female gamete. The process involves the fusion of an oocyte with a sperm, creating a single diploid cell, the zygote, from which a new individual organism will develop. The elucidation of the molecular mechanisms of fertilization has fascinated researchers for many years. In this review, we focus on this intriguing process at the molecular level. Several molecules have been identified to play a key role in each step of this intriguing process (the sperm attraction from the oocyte, the sperm maturation, the sperm and oocyte fusion and the two gamete pronuclei fusion leading to the zygote). Understanding the molecular mechanisms of the cell‑cell interactions will provide a better understanding of the causes of fertility issues due to fertilization defects.

Figure 1

The events taking place in fertilization. (A) Sperm preparation-capacitation: Molecules (resact, speract) secreted from the oocyte, orient and stimulate sperm (guanylate cyclase). (B) Acrosome reaction: release of hydrolytic enzymes. The sperm via SED1 protein is connected to ZP3. (C) Fusion of sperm with plasma membrane of the oocyte: sperm pre-acrosin binds to ZP2. Proteins of sperm IZUMO, ADAMs 1, ADAMs 2, ADAMs 3 and CRISP1 bind to receptors on the oocyte (Juno, integrins, CD9, CD81). Other molecules identified playing role in gamete fusion are: Trypsin-like acrosin, spermosin, SPAM1, HYAL5, ACE3. (D) Cortical Reaction: Ca⁺² release/wave of Ca⁺² and formation of fertilization cone. Enzymes released by cortical granules, digest sperm receptors ZP2 and ZP3 (block of polyspermy). (E) Sperm chromatin decondensation to form male pronucleus: The oocyte nucleus completes the 2nd meiosis and eliminates the 2nd polar body.