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Conceptual Problems (continued)

By Melissa Hendricks

Still, thousands of sperm are a lot of sperm. But in the normal course of events, the egg accepts one and only one suitor. After one sperm enters, the egg somehow switches from signaling to sperm, "Come hither," to warning other sperm, "Don't touch me." Evans is searching for answers to how the egg activates this "cold shoulder" signal, formally called the "block to polyspermy."

In her office, Evans illustrates how the block works by drawing a diagram on a whiteboard. She sketches a large circle (the egg), and outside it draws the iconic oval head and long snaking tail of a sperm. As the sperm swims toward the egg, she explains, molecules on the egg's surface and molecules on the sperm's surface meet and fit together like a lock and key.

The sperm now must deliver its DNA into the egg's cytoplasm. This task requires penetrating two layers: a thick outer coat called the zona pellucida (ZP) and an inner layer known as the plasma membrane. First, the sperm releases an enzyme, which drills a hole in the ZP. The sperm slips through this outer coat, and then its membrane fuses with the egg's plasma membrane. The two separate membranes are now one, and the chromosomes of the sperm can now join with the chromosomes from the egg.

Although scientists have defined many of the details of the ZP's role in the block to polyspermy, says Evans, they know almost nothing about the plasma membrane's role. So she has focused much of her research there, specifically on the role calcium may play in the membrane block.

Researchers have shown that the fusion of sperm and egg releases an enzyme that triggers a series of reactions leading to a surge of calcium within the cytoplasm. "The release of calcium tells the egg, 'You're not an egg. You're an embryo,'" explains Evans. "It's a whole new ballgame now."

In her studies, Evans has found that the increased calcium facilitates the membrane block. But in subsequent studies she has also shown that calcium is not essential. Without calcium, an egg can still block multiple sperm from getting in, but it does so less efficiently. There may be no "magic bullet," Evans concludes. "Multiple pathways must feed into this switch."

Nor is it clear precisely how the membrane changes itself to become impenetrable to sperm, another question that Evans is pursuing in her research. The membrane's components may restructure themselves in a way that enhances the defense against sperm, something like shifting from a man-to-man defense to a zone defense strategy in basketball, suggests Evans, who is a big fan of college ball.

Why would a cell bother with such an elaborate scheme? Why not allow one extra little sperm to get in every once in a while? What's the harm?

In fact, says Evans, "it's not a fail-safe system." Sometimes one extra little sperm does get into the egg, and in such cases, the resulting embryo will contain three sets of chromosomes (one from each sperm and one from the egg), instead of the customary two. "Such 'triploidy' spells catastrophe," says Evans. About 10 percent of miscarriages have such a triple set of chromosomes, and most of those cases probably result from two sperm fertilizing the egg when the egg failed to establish its block to polyspermy. That's why better understanding the events involved in the block could help scientists find ways to avoid such failures or perhaps even suggest contraceptive designs that exploit it.

Of course, errors can occur at other stages in the process of fertilization and during the transition from egg to embryo. The elaborate process probably has hundreds of such opportunities. Any of those might manifest as infertility. "That's why it's so important to understand the normal process," Evans adds, "because then we can have insight into the causes when people are not able to get pregnant."

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