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The Gene That’s Key to Fertilization Uncovered

When it comes to attempting a successful pregnancy, talking about genes can be boring. And what does it mean for an infertile couple trying to have children? The answer is that a pair of genes recently discovered are the keys for a successful fertilization, and could be the basis for future infertility treatments.1

Egg Genes: The Keys to Sperm/Egg Union
Researchers from Rutgers University uncovered the genes, aptly named egg-1 and egg-2, that they say are required for egg to meet sperm and fertilize successfully. The genes are closely related to LDL cholesterol (the “bad” cholesterol in the body); the proteins they make are similar to LDL.

The study is published in the December 24 issue of the journal Current Biology. The scientists found that once the genes were absent, fertilization came to a screeching halt. “What we learn in studying fertilization is not only important for this event, but also for the functioning of other cells in our bodies and for understanding many of those processes,” explained Andrew Singson, PhD, an assistant professor in the Waksman Institute of Microbiology at Rutgers, who led the research.

Fertilization Can Help Answer Other Questions
Fertilization can be a key foundation for understanding how cells interact in the body because it is one of the most basic cell-to-cell interactions, Singson explained. In this study, he and his colleagues focused on a roundworm known as Caenorhabditis elegans, the first multicellular organism to have all of its genes discovered. The roundworm was also used because it serves as a very good model for people. The millimeter-long worm is also transparent, allowing a clear view of its internal structure.

Its reproductive biology is much different from humans, but its underlying gene processes are similar. The worms exist as males when they are young, producing sperm. But they switch to produce eggs as adults. So, the Rutgers researchers collected both eggs and sperm to study the fertilization process.

To test what would happen if the egg-1 and egg-2 genes were missing, Singson’s group both removed their normal function and used worms that lacked the genes. They discovered that in these cases, the worms became sterile because fertilization did not occur.

Normal sperm, they wrote, could not enter the eggs produced by worms that lacked the two genes.

'Groundbreaking' Findings
The traditional scientific approach to studying fertilization has been to collect sperm and eggs, and then separately study their components, in an attempt to understand how they might function in fertility. While Singson admits that this has been productive, he says only definitive conclusions can be drawn by completely removing the genes necessary for fertilization, and then watching what happens.

“If you get infertility, then you know that the [gene] is required for fertility, and this is our ‘smoking gun’,” he explained. “Basically, we are asking the animal to tell us what it requires for its fertility, and then we try to understand how it works on a molecular level.”

He says this approach is unprecedented. “Our use of this genetic approach, which hasn’t been generally done in the past, is, indeed, groundbreaking.”

Singson’s team picked the egg-1 and egg-2 genes by using educated guesses based on Singson’s previous research that focused on sperm genes.2 When abnormal changes were made in those genes, sperm were unable to fertilize eggs. The hope was that the sperm genes, together with the newly discovered egg genes, would be the ‘lock’ and ‘key’ that contribute to normal fertilization. The latest study confirmed that the egg genes, indeed, play a key role.

“Ultimately, it will be exciting to determine if defects in similar molecules can lead to human infertility,” Singson said. 

1. Kadandale P, Stewart-Michaelis A, Gordon S et al. The egg surface LDL receptor repeat-containing proteins EGG-1 and EGG-2 are required for fertilization in Caenorhabditis elegans. Curr Biol 2005 Dec 24;15(24):2222-9.
2. Geldziler B, Chatterjee I, Singson A. The genetic and molecular analysis of spe-19, a gene required for sperm activiation in Caenorhabditis elegans. Dev Biol 2005 Jul 15;283(2):424-36.

John Martin is a long-time health journalist and an editor for CuraScript. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

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