The Chemical Signals Underlying Fertlization

Progesterone is a steroid hormone produced by the ovum and placenta, making it female-specific. Progesterone is responsible for preparing the uterus for pregnancy, but research published in the journal Nature in March 2011 identified another role for the hormone – conception.

For decades mystery has surrounded exactly how sperm seek out an egg for fertilization, a necessary step for conception. Unlocking the mechanism could lead to additional methods of overcoming fertility and, on the other side of the coin, preventing unwanted pregnancy via new types of contraception. The cation channel of sperm (CatSper) family of ion channels on mammalian sperm was first discovered in 2001. The CatSper are calcium channels unique to the tail of sperm. In 2009, a method of measuring the ion flow through the channel, via electrical conductance, was first used at the University of California San Francisco (see TheScientist for details on the method), allowing researchers to investigate its activation and effects. In 2010, the role of this calcium channel was found to be essential for sperm motility and male fertility via activation by physiological stimuli – but the question remained: how do sperm seek out an egg?

A few months later, in March 2011, the picture suddenly became much clearer. A research group in Germany found that progesterone, which is released by cumulus cells surrounding the egg released from the ovary, directly activates calcium ion flux through the CatSper channel, increasing sperm motility, and even enhancing the motility induced by other factors (see study abstract). Another research group at the University of California San Francisco found this same response, but elaborated that the progesterone-induced physiological response of the sperm included acrosome activation and the attraction of the sperm to the egg.

The acrosome is important because it is responsible for the sperm being able to penetrate or fuse with the egg, resulting in fertilization (i.e. the process of conception). The picture that this research has painted is as follows: While the stimuli near the egg, such as progesterone, activate sperm tail motility via the ion channels, the head of the sperm is directed at the egg. The head of the spermatozoa is capped, with the acrosome, an extension of the Golgi apparatus (an organelle response for protein packaging and trafficking within a cell). Contact with the outer membrane of the egg results in the release of enzymes from this cap that degrade the ovum’s outer layer, allowing the genetic material of the egg and sperm to meet (the acrosomal reaction). The exact specifics of penetration and/or fusion differ by species, but it all has the same general idea – fertilization, which now appears to be at least partly driven by progesterone.