Doctors in Japan have uncovered the processes surrounding fertilization at the molecular level, publishing a new study on their discoveries.1 While the findings may not have immediate benefits for people with infertility, the researchers claim this study could pave the way for new treatments for infertile men in the future.
"Representing the 60 trillion cells that build a human body, a sperm and an egg meet, recognize each other, and fuse to form a new generation of life," wrote Masaru Okabe, PhD, with the Genome Information Research Center at Osaka University in Osaka, Japan, and his team of investigators. "The factors involved in this important membrane fusion event, fertilization, have been sought for a long time."
An Essential Protein is the Key
At the heart of this sperm/egg fusion is a vital protein located on the surface of sperm. Without it, Okabe and his colleagues wrote, fertilization is not possible. This protein is synthesized by a gene that the scientists call Izumo, named after a Japanese shrine dedicated to marriage.
This study built on recent research involving animals that found that a counterpart protein dubbed CD9—located on the surfaces of eggs—was essential for sperm and egg to unite.2,3 Now, the latest study discovered for the first time that this gene produces a counterpart protein on the surface of sperm, which plays a similar role in fertilization.
After discovering the gene and the protein activated by it on sperm, Okabe's team wanted to confirm their theory that the protein is the key to a successful fertilization. They studied mice engineered to lack the Izumo gene to find out what happened next. The rodents "were healthy, but males were sterile," the scientists wrote. "They produced normal-looking sperm that bound to and penetrated the zona pellucida [an egg's outer membrane], but were incapable of fusing with eggs."
Finally, the research group tested human sperm, which they say also contains the essential gene, with a group of eggs. Removing the gene from the human sperm also left them unable to penetrate the eggs, the scientists wrote.
The Focus on Fertilization Processes
Similar to this research, doctors elsewhere have zeroed in for many years on the mechanisms behind successful fertilization in hopes of contributing to medical science that could lead to treatments that are more effective or improved assisted reproductive technologies (ART) for couples diagnosed with infertility.
For example, a study by Japanese doctors at Tokyo University of Agriculture and Technology published last year4 focused on the nuclei of sperm that failed to fertilize eggs in a series of intracytoplasmic sperm injection (ICSI) techniques. This is a clinical procedure designed for couples with severe male factor infertility or in men diagnosed with azoospermia, or the absence of sperm.5
For the research, the investigators performed ICSI on a group of mouse eggs, then looked for any chromosomal abnormalities that might be present.
And a review published last year described some of the molecular mechanisms surrounding fertilization, including the discovery of a family of proteins that play a role in the binding of sperm to the egg just prior to fertilization.6
The scientists from the University of Edinburgh in Scotland wrote: "Sperm-oocyte fusion is one of the most impressive events in sexual reproduction, and the [understanding] of its molecular mechanism has fascinated researchers for a long time."
1. Inoue N, Ikawa M, Isotani A, Okabe M. The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature 2005 Mar 10;434(7030):234-8.
2. Li YH, Hou Y, Yuan JX et al. Localization of CD9 in pig oocytes and its effects on sperm-egg interaction. Reproduction 2004 Feb;127(2):151-7.
3. Kaji K, Oda S, Miyazaki S, Kudo A. Infertility of CD9-deficient mouse eggs is reversed by mouse CD9, human CD9, or mouse CD81; polyadenylated mRNA injection developed for molecular analysis of sperm-egg fusion. Dev Biol 2002 Jul 15;247(2):327-34.
4. Araki Y, Yoshizawa M, Abe H, Murase Y, Araki Y. Use of mouse oocytes to evaluate the abilty of human sperm to activate oocytes after failure of activation by intracytoplasmic sperm injection. Zygote 2004 May;12(2):111-6.
5. Al-Hasani S, Ludwig M, Palermo I et al. Intracytoplasmic injection of round and elongated spermatids from azoospermic patients: results and review. Hum Reprod 1999 Sep;14 Suppl 1:97-107.
6. Kaji K, Kudo A. The mechanism of sperm-oocyte fusion in mammals. Reproduction 2004 Apr;127(4):423-9.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
