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Conceptual Problems

When sperm meets egg, most people can guess the result. Janice Evans hopes discovering how and why will lead to better contraceptives and solutions to infertility.

By Melissa Hendricks

As romantic places go, it isn't much: A plastic room with transparent walls. No privacy to speak of. But the amorous sperm and eggs floating in the pink culture medium in this petri dish don't seem to mind. They're going at it full bore.

At least the sperm are. Several of these tiny dark commas wriggle, spin and jerk feverishly on the egg's surface. The egg, gargantuan next to the sperm, just floats like a placid balloon, occasionally drifting this way and that in response to the sperm's flailings.

We may associate sex with romance, hearts and roses. We may think of it as a triple X event. Or we may view it as a way to transcend our ordinary daily lives. But take away the sonnets and champagne, and it's fundamentally a matter of biology: a tiny comma tapping at a puffy orb.

A pair of eyes—a voyeur's enormous eyes—stare down at the sperm and egg through the peephole of a microscope. The eyes belong to Bloomberg School biologist Janice Evans, PhD, who uses in vitro fertilization (IVF) for her research and is in the process of teaching the skill to Hopkins freshman Luccie Wo.

"One thing that is really remarkable about the fertilization process is that if an egg doesn't get fertilized, it goes off and dies," says Evans, an associate professor of Biochemistry and Molecular Biology. "If a sperm doesn't fertilize an egg, it goes off and dies. But if these two cells get together, they are going to become the building block that builds every cell in our body. So it's pretty freakin' remarkable."

Scientists have known for more than 100 years that new life begins with the union of sperm and egg. Now, biologists like Evans are seeking to understand this event even more intimately. Her colleagues in Biochemistry and Molecular Biology include professors William Wright, who works down the hall from her and has spent two decades studying a gene involved in sperm development, and Barry Zirkin, who also studies sperm development, particularly aging's effects on it. These researchers want to know not just what happens but why, to define the mechanism of sex down to its molecular essence.

Beyond the beauty and elegance of the systems they study, Evans and others in the field are excited by the idea that their findings could help advance medicine and benefit public health. As the world's population climbs toward 7 billion, reproductive health experts continue to seek ways to expand the use of family planning. But obstacles to wider contraceptive use remain, including women's concerns about the side effects and inconvenience of various methods.

That's where research like hers could help, says Evans. Elucidating the molecular details of fertilization could suggest designs for new contraceptive choices. She and other researchers envision a contraceptive drug that would bind to precise "molecular targets" on the egg or sperm. A drug, for example, might attach to a molecule on the egg's surface where sperm normally bind, suggests Evans, "so there would be no parking places for sperm." And if the drug targeted molecules found only on the egg—and nowhere else in the body—it might produce fewer side effects than hormone-based contraceptives, which can lead to a variety of symptoms, ranging from breast tenderness to more serious (and rarer) health problems like stroke and blood clots.

Studies of egg and sperm may also advance doctors' ability to diagnose and treat infertility. In the U.S., infertility affects about 10 percent of people in their reproductive years, but a large fraction (perhaps 20 percent) of infertile couples have no apparent cause for their inability to conceive.

But you won't find any human eggs or sperm in Evans' lab, only those of mice, her model for mammalian reproduction. And at this moment she is training Wo in the fine art of IVF, a skill that requires a steady hand and good eye-hand coordination. "I never get tired of it," Evans says, pulling away from the microscope. "It's always fun."

Yesterday, Wo pipetted eight mouse eggs and added them to a petri dish containing about 1,000 sperm. Then she left the gametes to do their thing. If all goes well, the frolicking now under way in the dish should, in the next two hours, lead to fertilization and signs of an egg becoming an embryo.

Evans does not recall exactly when she first learned the details of fertilization (probably in junior high biology class, she says). In any case, these facts only generated more questions for her, ones that she now pursues in her research lab. How do the sperm and egg come together, and how do those interactions cause the egg to block more sperm from getting in? Why does this dance involve only two partners and not more?

During sexual intercourse, a man normally ejaculates tens of millions of sperm. Most of those sperm will have no chance of completing the marathon swim to the egg. Some will perish upon encountering the vagina's acidic environment. Others will lack tails or the strength to swim far. Still others will fatally propel themselves into a dead-end crevice of the female reproductive tract. Only thousands of the original millions of sperm, Evans estimates, will get close enough to have a shot at fertilizing the egg.

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