Molecular mechanisms leading to gamete fusion

Abstract

The fusion between spermatozoon and oocyte represents the final stage of fertilization in mammals. Since only one of the extremely large number of spermatozoa fertilizes the oocyte, there should be a strictly regulated molecular mechanism in gamete fusion. Oocyte CD9 was first identified as a key factor for gamete fusion, followed by sperm IZUMO1 and oocyte IZUMO1 receptor JUNO. Since 2020, with the recent emergence of genome editing technologies, new gamete fusion sperm factors, SPACA6, TMEM95, FIMP, SOF1, DCST1, and DCST2, have been reported one after another. In this review, I would like to give an overview of mammalian gamete fusion based on the latest findings on these factors.

Keywords: Fertilization; Gamete fusion; IZUMO1; Oocyte; Spermatozoon.

Fig. 1.

IZUMO1, JUNO, and DCST1/2 are all essential for gamete fusion in mammals. (A) Localization of IZUMO1 before and after acrosome reaction. When the acrosome reaction is triggered with exocytosis, soluble proteins and matrix (green) within the acrosome are released externally and transmembrane IZUMO1 (red) quickly moves to the surface of the sperm head, including the equatorial segment. (B) Tertiary structure of the IZUMO1-JUNO complex. The monomer IZUMO1 exposed on the sperm surface recognizes the monomer JUNO, the IZUMO1 counter receptor, on the oocyte surface, and as a result, spermoocyte adhesion begins. Tertiary structure analysis based on X-ray crystallography has revealed the interaction mode of the IZUMO1-JUNO complex. (C) DCST1/2-deficient mice are male sterile due to failure of gamete fusion. Spermatozoa from DCST1/2- deficient mice have normally undergone the acrosome reaction, a morphological change in spermatozoa (red: IZUMO1), but are unable to fertilize, multiple spermatozoa are present in the perivitelline space between the zona pellucida and the oocyte.