It’s the carrot in front of the mule and the cake in front of the child: individuals are drawn to reward. But surround them by that reward — a mule in a field of carrots, a child in a cake shop — and behaviour switches from unidirectional to hyperactive. The greyhound that focuses on the moving rabbit wins the race: the greyhound that gets distracted by rabbits in the field next door may one day reach the finish line, but not because of the lure.
So it is in biology. Chemotaxis, the process by which cells and bacteria move according to certain chemicals in their surroundings, relies on a gradient of attractive or repulsive cues to cause directed movement. Surround a cell by growth factors and it will grow in all directions, but form a gradient in one direction only and it will grow that way. This is how nerves form complicated networks throughout the body, wrapping around other structures, and it is how good sperm find an egg.
Despite technological advances, fertility treatment remains inefficient, with about a 30% success rate. The hurdle of poor sperm quality has not been overcome. Fertility treatment is also expensive and has a deep emotional cost.
Now, researchers at the Universidad de Córdoba in Argentina have developed a method for separating good sperm from poor sperm, offering hope for the improvement of assisted reproductive technology, and it’s all down to that single carrot, dangled before the mule.
Egg cells mature within a cluster of cells called cumulus cells, which are essential for the egg’s development and protection. One of the many jobs of the cumulus cells is to kick out the steroid hormone progesterone. Sperm react positively to gradients of very low amounts of progesterone, but, like the child in a cake shop, go wild if surrounded by too much. It also happens that the cells that respond most efficiently, and less chaotically, to the very lowest concentrations of progesterone are the very best sperm, the ones that would, given the opportunity, competently fertilize an egg. This new study from the laboratory of Prof Laura Giojalas takes advantage of this behaviour.
Their device, called the sperm selection assay (SSA), takes only 20 minutes to operate, using a low concentration progesterone gradient between two small plastic dishes, between which the sperm swim. After this time, the collected sample contained three times as many high quality sperm cells than both normal and poor quality starting samples. In addition, with only a 20 minute run time, the experiment can be repeated to further improve sample quality. Purified sperm from the SSA also had reduced DNA damage.
The SSA was particularly effective when run on extremely poor quality starting samples, where the level of high quality cells could be increased by up to 11 times.
These are still early days — having more good cells per sample still does not guarantee fertilization — but the SSA is a helpful step towards overcoming this hurdle in human fertility treatment.
Gatica, L. V. et al. Picomolar gradients of progesterone select functional human sperm even in subfertile samples. Mol. Hum. Reprod. epub 31 May 2013