Sperm tails reveal clue to non-hormonal contraceptives for either sex

CatSper is a protein found only in those whiplike tails, and it controls electrical currents in sperm. Blocking it could render sperm sterile.
Written by Janet Fang, Contributor

How does sperm know to swim towards the egg?

Two new studies that reveal the molecular mechanism behind how sperm detect eggs could help the development of a new class of contraceptives – ones that are non-hormonal and could work in either sex.

Scientists know that cells surrounding an egg awaiting fertilization in the fallopian tubes releases progesterone – a female sex hormone. Somehow, it guides sperm toward the egg. It even causes sperm to whip their tails more forcibly – something called hyperactivity – which frantically propels them through the thick jelly coating of eggs.

Now, two teams – from the University of California San Francisco and from Germany – independently show that progesterone activates a protein known as CatSper.

In humans, CatSper is a channel that ferries calcium ions in and out of sperm. With progesterone, it rapidly inundates sperm with calcium ions. But sperm without CatSper can’t become hyperactive.

"CatSper is viewed as one of the best targets in a new class of contraceptives," says Polina Lishko from UCSF.

The teams developed methods to measure the electrical signals within sperm created by ions like calcium. Adding progesterone to ejaculated human sperm boosts the electrical current, whereas treating the sperm with CatSper-blocking drugs reduces it, Nature explains.

A decade ago, researchers discovered that infertile mice and men sometimes had mutations that disrupted CatSper. These new findings may help explain the 40% of male infertility cases where cause is unknown, according to Benjamin Kaupp of the Center of Advanced European Studies and Research, who led one of the teams.

He adds: "It could be that some eggs do not produce enough progesterone, or that some sperm are not as sensitive to progesterone as others."

Nature reports:

Yet there would be little demand for infertility drugs that activate CatSper, says Kaupp, because infertility is already well-addressed by in vitro fertilization. More promising, say researchers, are drugs that stymie conception by hindering the channel's ability to sense progesterone – or to work at all.

And, it would be a non-hormonal contraceptive – unlike current female contraceptives that depend on progesterone or estrogen and affect other things like weight and sex drive.

Since sperm tails are the only places known to have CatSper, a drug that blocks it would be unlikely to have side effects elsewhere.

It would also, presumably, work regardless of whether it is men or women who take it because it could act on sperm regardless of their location, according to Lishko.

Once researchers have located where progesterone binds to the CatSper channel, she adds, they can look for molecules that would block this interaction, rendering sperm sterile.

Both studies appear in Nature this week.

Image: Carin Cain

This post was originally published on Smartplanet.com

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