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How Does Sperm Get Into That Egg?

The words 'successful fertilization' is always joy to the ears of infertile couples who want to become parents. But how does that life-building process actually occur? We know this happens when one sperm penetrates the egg, but if you could take a very powerful microscope and watch the process, what really happens?

And why should we care? Medical experts say understanding the process could help them develop ways to actually enhance fertilization one day. For those who've undergone a series of failed cycles, this would be good news.

Diving Down to the Molecular Level
Scientists at the Howard Hughes Medical Institute, an international non-profit research organization, decided to delve into the process to gain a better understanding. Their findings are published in this month's issue of the journal Public Library of Science Biology.1

In the study, Luis Mayorga, PhD, an assistant professor in the Institute of Histology and Embryology at the National University of Cuyo in Argentina, and his colleagues followed the processes involved in the sperm's penetration of the egg. The sperm produces a group of enzymes that "eat away" at the outer membrane of the egg, allowing the sperm to enter. "Because the sperm has a single opportunity, this secretion has to be very well-regulated," Mayorga explained. "If the sperm doesn't respond right on time, it won't get through the egg's coating."

Enzymes Help Sperm Enter the Egg
Inside the sperm, the enzymes sit, waiting for their big, one-time performance. They're housed in a section of the sperm known as the acrosome (ACK-roh-soam), which is surrounded by its own membrane. During fertilization, the acrosome's membrane joins with the sperm's outer membrane—a process that results in the enzymes being released outside the sperm. This is similar to the process by which a bubble rises to the surface of a soda, and releases its gas into the air.

The research team also evaluated the molecules that are involved in this process of fusion. They're called SNAREs, and work somewhat like Velcro to hold membranes near each other so that they can eventually stick together. In sperm, the membrane of the acrosome, where the enzymes ready to eat away at the coating of the impending egg sit in waiting, contain one type of SNARE, and the sperm's outer membrane contain another type.

Both types of SNAREs are tightly stuck to each other, as is their counterpart molecules. So, in order for the enzymes that eat a hole in the outer membrane of the egg to be released from sperm, each SNARE group must be broken apart so that they can be paired with their counterparts. This happens when calcium enters the sperm.

Introducing an Unnatural Intervention
During their experiments, Mayorga's team observed SNAREs sticking together on the two membranes (the sperm's and the acrosome's), which would normally lead up to the release of enzymes. Instead, they altered the process, delivering  poisons into the scenario. Some, but not all of these toxins, blocked this membrane union from happening. They found that the SNAREs were not completely unlocked from each other, which would make them more vulnerable to the poison, nor were they tightly clamped together in their final, tight configuration, which would make them resistant to the toxin.

A tight-fitted group of SNAREs only forms—and thus, the sperm and acrosome's membranes unite—once sufficient amounts of calcium enter the acrosome. Once this happens, the two membranes fuse together, forming a pore that releases the enzymes from the sperm, at which point they begin digesting the egg's outer surface.

"In our experiments, it is very clear that those complexes have a loose form and are waiting for calcium to complete fusion," said Mayorga.

Enhancing Knowledge About Fertilization
Many of these factors involved in releasing the sperm's enzymes when it meets up with the egg will be essential for manipulating fertilization, the scientists point out. In the case of infertile couples, giving a boost to the sperm and egg at the point at which they unite would likely be the most desirable.

The steps leading to the sperm's penetration of the egg studied in this research "is a central process in sperm physiology, and understanding the molecular mechanisms underlying it will be out outstanding importance for our ability to regulate fertilization," the research team concluded.

1. Blas GA, Roggero CM, Tomes CN, Mayorga LS. Dynamics of SNARE assembly and disassembly during sperm acrosomal exocytosis. PLoS Biol 2005 Sep 6;3(10):e323 [Epub ahead of print].

John Martin is a long-time health journalist and an editor for Priority Healthcare. 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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