Scientists first started putting semen under a microscope almost 350 years ago, and ever since, their sperm sightings have produced as many questions as answers. Back then, they couldn’t figure out exactly what the squirmy little things were, or what they did, let alone the different ways across the animal kingdom that sperm carry out their reproductive role.
Part of the problem stems from looking in the wrong place. Sperm don’t do much under a microscope; they thrive once in the female reproductive tract—a very difficult place to see what happens when squads of sperm go into action. The situation has produced some enduring misconceptions, like the idea that reproduction is always an “every sperm for itself” sprint.
Despite the often-competitive aspects of animal reproduction, scientists now know that some groups of sperm from the same ejaculate actually congregate to work together in a kind of social cooperation. Researchers have recently documented the sperm of mice, mollusks and opossums joining forces, though they don’t always know why that happens.
A study published today in Frontiers in Cell and Developmental Biology has revealed a reason, among bulls at least; swimming together helps sperm move through the gooey fluids found on their migration through the female reproductive tract. Using a microfluidic machine to simulate the mucous-like conditions inside a cow, researchers learned that clustering sperm have advantages that help them efficiently navigate the female tract and swim upstream against the flow—better than single sperm. The study, and others seeking to recreate the environments in which sperm swim, may help improve sperm analysis that might be used to boost human fertility techniques.
Sperm science has a long and colorful history. The field was launched by Anton van Leeuwenhoek, inventor of the compound microscope, who observed sperm in his own semen and published a paper of his findings in 1678—albeit only after worrying that “these observations may disgust or scandalise the learned.” Once van Leeuwenhoek brought sperm into the limelight, many sometimes comical theories attempted to explain what exactly sperm were and how conception occurred. His contemporary Nicolass Hartsoeker claimed to have seen sperm a few years before van Leeuwenhoek’s publication but, like others afterwards, he dismissed them as a type of seminal parasite. For nearly two centuries a school of thought insisted that each sperm contained a very tiny, preformed human.
Sperm are single cells with a unique mission. They pass on a male’s genetics to the next generation. Unlike any other cells, they aren’t meant to be part of the body but instead are produced to be ejaculated and live in a foreign environment. “Our main field site is the female reproductive system, but it’s an incredibly difficult place to visualize and do experiments,” says Scott Pitnick, a Syracuse University biologist and sperm specialist not involved in the study. “It’s probably easier to study icefish in the Antarctic.”
Chih-kuan Tung, a physicist at North Carolina Agricultural and Technical State University, and colleagues tackled that problem by recreating important aspects of the female reproductive system so that sperm might be easily observed. Tung notes that in a typical fertility clinic, or a service trading in bull semen, researchers simply put sperm into a watery lab solution, sandwich it between two pieces of glass, and watch them swim under a microscope. While the method reveals obvious problems, like sperm that can’t swim, it can’t provide much real-world information.
“We should really look at a swimming environment closer to what sperm would encounter in a female reproductive system,” notes Tung. To that end his team from North Carolina A&T and Cornell University began studying how bull sperm—a decent stand-in for our own among the mammals—moved in a gooey environment akin to conditions in the bovine cervix, uterus and oviduct.
The group knew from previous research with the fluid that bull sperm formed clusters, but also that those clusters couldn’t swim faster than individuals, so that obvious advantage wasn’t the reason the sperm stuck together. In search of another advantage, the team designed a new experiment that added flows or currents, like those the sperm encounter in life. They uncovered three different ways sperm benefitted from clustering, depending on the flow of the fluid in the environment.
When there was no flow, the clusters moved forward in a far more direct path towards their target than individual sperm were able to do. “That’s an advantage for them, because they want to go somewhere,” Tung explains.
At moderate flow levels, clustered sperm were better able to align themselves to swim directly against the flow. That’s the direction they desire to go in the female tract, because fluid would generally head outward.
When flow current levels were turned up to the highest levels found inside the reproductive tract, clustering enabled sperm to stand strong and withstand the flow, so that they were swept away downstream far less frequently than individual sperm were.
Together, the results show that the sperm’s journey through reproductive tract fluids is aided by social cooperation. They can more efficiently identify and maintain proper direction or even, in strong currents, use drafting techniques favored by packs of cyclists and racecars.
By trying to mimic the environment of the female tract, from fluid flows to three-dimensional shapes, studies like this one may improve semen analysis and help to create more effective infertility treatments for humans—as well as better contraception for those hoping to avoid pregnancy.
“People are going to more realistic sorts of environmental setups for exploring sperm function, and that’s been completely missing in the history of sperm research,” says Pitnick. In his own work with fruit flies, he uses fluorescent protein tagging to make sperm heads visible so that he can observe how they interact and compete in the female reproductive tract.
Among species other than bulls, research has uncovered some instances of social cooperation in which the sperm move collectively in some very interesting ways. Each wood mouse sperm has a hook on its head, by which the sperm connect into trains of hundreds to thousands that swim faster than individuals. In some mollusks, one outsized sperm serves as a kind of mobile penis, a bus that transports and drops off other fertilizing sperm on its route through the reproductive tract. In the opossum, sperm have evolved to get where they are going by swimming in pairs, linked by asymmetrical heads, only separating when they are close to an opportunity to fertilize the egg. But scientists don’t yet know all of the reasons these sperm cells cooperate. In teasing out some definite advantages among bull sperm, this study moves the ball forward.
“To me this study shows that it’s probably the case that even in species that haven’t evolved mechanisms of physically binding together for this cooperation, there are still benefits for sperm cooperating during their migration through the female tract,” says Pitnick. “And they demonstrate in terms of biophysics, flow dynamics, how this actually works.”
Such work is also key to understanding the evolutionary biology of sperm, how they have come to function in amazing and unique ways inside of the female reproductive tract—which Pitnick calls one of the great unexplored frontiers in all of biology. “We have to understand that environment,” he says, “to understand what sperm do in it.”