Sperm Wars: Lily of the Valley Revisited

One of the stranger stories in olfactory science is the apparent ability of mammalian sperm to respond to the odorant bourgeonal, which to the human nose smells somewhat like lily of the valley. Speculation has been that this pleasant floral scent is also a secret signaling molecule that guides sperm to the egg, by activating the odorant receptor OR1D2 located on the sperm cell’s surface.

Adding to the strangeness is the fact that, unique among odorants that have been tested, men are more sensitive to bourgeonal than are women. Men more sensitive to bourgeonal, sperm able to detect it—there seemed to be a compelling narrative.

Now it appears that the entire lily of the valley story needs to be rewritten.

Back in 2011, researchers led by Timo Strünker at the Center of Advanced European Studies and Research, in Bonn, Germany, took a closer look at the biochemistry of sperm, specifically at the mechanism underlying the progesterone-induced calcium ion (Ca2+) influx. The calcium influx activates a number of key physiological responses in sperm, including chemotaxis. The thought had been that a cell-surface receptor activated by progesterone kicked off a series of biochemical reactions leading to the opening of the CatSper Ca2+ ion channel. Once the channel is open, calcium ions flood through and into the sperm cell.

What Strünker and his colleagues demonstrated in their paper in Nature is that the CatSper channel is not opened by activation of a separate progesterone receptor. Instead, the CatSper channel itself (or an associated protein) serves as the progesterone receptor. (To anthropomorphize a bit: if you a progesterone molecule, you hold the key that opens the door directly; you don’t need to ring a doorbell down the hall and have someone open the door for you from the inside.)

While of interest mostly to biochemists, the Nature paper was a warning shot over the bow of Team Bourgeonal. It meant that separate, specialized receptors, such as odorant receptors, were not necessary for the calcium influx. In 2012, Strünker and team fired directly amidships. In an intricate and exhaustive set of experiments, they showed that the CatSper channel is activated by all sorts of molecules, including steroids, prostaglandins, menthol, bourgeonal, and several other odorants such as cyclamal, helional, and undecanal.

In other words, you can activate the CatSper channel by looking crooked at it. Or, as the researchers put it, “Activation happens through promiscuous, extracellularly accessible site(s) either on the channel itself or on associated proteins.” And this activation takes place completely independent of any odorant receptor for bourgeonal.

Team Strünker hypothesizes that the promiscuous CatSper channel “serves as a polymodal sensor for multiple chemical cues that assist sperm during their voyage across the female genital tract.” The idea that sperm are specifically attracted to bourgeonal’s lily of the valley scent is, it seems to me, dead in the water.

The studies discussed here are “The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm,” by Timo Strünker, Normann Goodwin, Christoph Brenker, Nachiket D. Kashikar, Ingo Weyand, Reinhard Seifert, and U. Benjamin Kaupp, published in Nature 471:382-386, 2011, and “The CatSper channel: a polymodal chemosensor in human sperm,” by Christoph Brenker, Normann Goodwin, Ingo Weyand, Nachiket D. Kashikar, Masahiro Naruse, Miriam Krähling, Astrid Müller, U. Benjamin Kaupp, and Timo Strünker, published in EMBO Journal, 31:1654-1665, 2012.