Genetics May Guide New Infertility Therapies

• Professor Singson’s Web Site
  

• The Singson Laboratory

• The Waksman Institute of Microbiology

• The journal Current Biology
  

One in six couples worldwide experiences fertility problems and fertility rates are dropping across the developed world. People are asking why, and Rutgers geneticists are beginning to find answers. Their groundbreaking discovery of two genes required for fertilization, aptly named egg-1 and egg-2, is reported in the journal Current Biology.

A critical first step in fertilization is for a sperm to enter an egg. To do so, the sperm has to recognize the egg and ignore other sperm or cells in the environment. Then there are interactions needed to get the surface membranes of both sperm and egg to fuse.

A team led by Andrew Singson, an assistant professor, and graduate student Pavan Kadandale, turned to the lowly roundworm Caenorhabditis elegans, the first multicellular organism to have had its genome completely sequenced, to unravel the mysteries behind the fertilization process.

The millimeter-long worm is transparent, allowing a clear view of its internal workings, and its short life cycle permits researchers to chronicle developmental and hereditary factors over generations. These properties have enabled researchers to use the worm for discoveries ranging from cell death and life span regulation to nervous system structure and function.

But the worm’s most important attribute as a model for this work may be its curious reproductive biology. These worms exist as males or hermaphrodites. When hermaphrodites are young they produce sperm and switch to produce eggs as adults.

The Rutgers scientists employed genetic tools, such as RNA interference and gene “knockout” mutants, to see what would happen if worms lacked the function of egg-1 or egg-2 genes. The researchers altered eggs in the hermaphrodites and used sperm from young males to test fertilization. The result was that worms became sterile because fertilization had failed to occur; normal sperm could no longer enter the eggs produced by egg-1 and egg-2 mutant hermaphrodites.

“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,” Singson said. The underlying cell biology, he said, is going to be universal with applications even in infectious diseases, such as AIDS, where the virus passes its genetic material to the cells it infects just as fertilization transmits sperm DNA to the egg.