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Sperm's egg-seeking secrets revealed
Sperm may be fast and hard to pin down, but scientists have uncovered the mechanism behind how these cells zero in on an egg and fertilise it.

The discovery could lead to the development of non-hormone based contraceptives for men and women that don't have side-effects.

For more than two decades scientists have known that the sex hormone progesterone, released from ovulated eggs, stimulates the flow of calcium ions (Ca2++) in sperm. This reaction helps sperm identify and swim toward the egg, as well as break through the egg's protective covering to fertilise it.

But scientists were unsure about how progesterone did it.

According to two studies published in this week's issue of Nature, progesterone activates a calcium ion channel, known as CatSper, which is found in the sperm's tail or flagellum.

Researchers from the University of California San Francisco studied sperm cells using a technique they pioneered called sperm patch-clamp technique.

The sperm is pinned down between the head and the tail, where the cell membrane is softer, using a glass pipette. A small hole is punctuated through the membrane and the material inside the cell is replaced by a solution. Calcium ions were then "passed through" the CatSper channel to create an electrophysiological fingerprint.

"By studying the CatSper channel electophysically in isolation from all other ion channels or transporters, we were able to prove that the CatSper channel is activated by progesterone and is the long-sought elusive progesterone receptor of human sperm", says study lead author Dr Polina Lishko.

In the second study appearing in Nature, German researchers observed sperm loaded with calcium-sensitive fluorescent dye to detect the presence of calcium ions, in addition to the patch-clamp technique, and reached a similar conclusion.

"Although we don't know the exact binding site for progesterone, we can conclude that progesterone binds to the CatSper channel itself or to a directly associated protein," says lead author Dr Timo Strünker of the Center of Advanced European Studies and Research in Bonn.
Impact on fertility

The research findings are hugely significant, says Lishko, because mutations of the CatSper channel, are known to cause complete male infertility.

"Without it [the CatSper channel] sperm cannot penetrate the protective vestments of the ovulated egg and cannot fertilise it."

As the CatSper channel is found nowhere else in the body except sperm it offers the potential to develop specifically targeted contraceptives, she says.

Unlike traditional hormone-based contraceptives, which target the progesterone receptors in all the body's cells causing side effects such as weight gain, abdominal cramps and mood swings, the binding site for progesterone on the CatSper channel is unique.

"Therefore potential development of unisex contraceptives which target a molecule unique for the sperm ... is possible, says Lishko.

"Such a contraceptive should have minimal side effects, because it will target the molecule not present in the female body, only in the male body, and only on sperm."
Important milestone

Professor John Aitken director of the ARC Centre of Excellence in Biotechnology and Development says both papers are an important finding in the field of reproductive cell biology.

"People have tried for many years to understand the nature of the receptor for progesterone. Several people have published papers saying that they have identified said molecule, but none of those identifications have really stood the test of time.

"So these two papers are certainly a milestone in the field," says Aitken.

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