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Timo Strünker, Normann Goodwin, Christoph Brenker, Nachiket D. Kashikar, Ingo Weyand, Reinhard Seifert & U. Benjamin Kaupp
The CatSper channel mediates progesterone-induced Ca21 influx in human sperm

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Cell Biology

Female sex hormone controls human sperm

Progesterone activates sperm-tail calcium channels to control the sperm’s swimming behaviour

March 16, 2011

In some relationships, the male takes the steering wheel. At cellular level, however, when the egg encounters a sperm cell, the female is the one at the controls. Scientists from the center of advanced european studies and research (caesar) in Bonn are now able to explain the mechanism by which the female sex hormone progesterone acts on human sperm. Benjamin Kaupp and his team have reported in the current issue of the journal Nature that the hormone activates sperm-specific CatSper (cation channels of sperm) ion channels to control the swimming behaviour of the sperm.
The female hormone progesterone (green) affects the CatSper ion channels  (red) in the tail of the sperm, which then allow calcium ions (yellow)  to flow into the sperm. Thus, the CatSper channels and progesterone form  an important part of the navigation system that leads the sperm to the  egg.<b> </b>
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The female hormone progesterone (green) affects the CatSper ion channels (red) in the tail of the sperm, which then allow calcium ions (yellow) to flow into the sperm. Thus, the CatSper channels and progesterone form an important part of the navigation system that leads the sperm to the egg. [less]

The egg or oocyte provides a signpost for the sperm in the Fallopian tube. To ensure fertilisation, cumulus cells, which surround the egg, release the female sex hormone progesterone. Progesterone serves as a chemoattractant and points the sperm the way to the egg.

In addition to its attracting effect, progesterone also serves another purpose: in the immediate proximity of the egg, where its concentration is highest, it triggers hyperactivation of the sperm. Hyperactive sperm beat their tails forcefully like a whiplash, and appear to mobilise their last reserves of strength – like marathon runners in the home stretch. This enables the sperm to penetrate the thick cloud of cumulus cells and the protective egg vestments. In human sperm, progesterone evokes an increase in the intracellular calcium concentration. These calcium signals alter the beating pattern of the sperm tail and thereby control the sperm’s swimming path.

The scientists from the Research Center caesar in Bonn have now discovered that progesterone acts on CatSper calcium channels. These ion channels are found exclusively in the membrane of the sperm tail. Ion channels are pore-forming proteins in the cell membrane that act as floodgates for ions. Progesterone opens the sperm-specific CatSper channels and calcium ions flow into the cell; as a result, the calcium concentration increases.

This discovery is remarkable in several respects. Despite decades of intense research, it has remained mysterious how progesterone triggers the calcium signals. Complicated models for the progesterone effect have been developed. The researchers in Bonn were themselves surprised at how simple the mechanism is: progesterone activates CatSper channels without involving second messenger.

In addition, the study provides new insight into the role of the CatSper channels in sperm. These channels control the swimming behaviour of the sperm – this has already been known. That the CatSper channels probably act as the receptor for the chemoattractant progesterone is astonishing. “It was only with the help of state-of-the-art electrophysiological and optical technologies,” explains Kaupp’s team member Timo Strünker, “that we succeeded in resolving the 30-year-old mystery of the progesterone action.” The Bonn-based researchers collaborated on the study with scientists from the Research Center Jülich.

“The discovery that progesterone activates the CatSper channels is also highly significant in medical terms,” adds Kaupp. “new contraceptives with fewer side effects disrupting the interaction of progesterone and CatSper could be developed.” However, the development of an innovative contraceptive from this scientific discovery is still a long way off.

caesar Foundation

The caesar Foundation is associated with the Max Planck Society and operates a neuroscience research centre in Bonn. The scientific work at caesar is carried out in accordance with the Max Planck Society’s criteria for excellence.

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