Riding the ‘Sperm Sensor’ Molecule to Improved Fertility

 

Among the frustrations experienced by couples seeking to conceive, perhaps none perplexes so much as a sperm cell’s inability to effectively make the journey to the egg in order for fertilization to occur.

After all, a number of factors that contribute to low fertility rates -- lack of exercise or too much exercise; exposure to industrial pollutants and household chemicals; and, fluctuations in diet -- can often be mitigated by taking appropriate steps.

But it’s not as though a man can improve a sperm’s motility as he would, say, his diet or exercise regimen, is it?

Breakthrough discovery?

Maybe not today, but someday the answer to the above question might well be Yes. A team of researchers, led by Jean-Ju Chung, assistant professor of cellular and molecular physiology at Yale University, recently announced that it had pinpointed a molecule that could play a pivotal role in helping sperm succeed in their journey to a female egg.

The findings of the research, which were published in the May 2, 2019 edition of the journal Cell, involve how sperm begin their trip to the ovum when changes are picked up in areas of their tails that, perhaps appropriately enough, have the appearance of racing stripes. The “stripes”, in this case, are actually calcium channels that open and close – pushing and guiding the sperm -- at the direction of the molecule that became the focus of the researchers’ efforts.

According to a press release, “When the gene that encodes for the molecule is removed through gene editing, male mice impregnate fewer females, and females who are impregnated produce fewer pups”. In addition, lab experiments also demonstrated that the sperm of the affected mice show less activity and wind up fertilizing lesser numbers of eggs.

Up to this point, studies had not succeeded in zeroing in on the specific mechanics in the calcium channel complex, known as CatSper, that permitted sperm to take cues from changes such as acidity levels throughout the female reproductive tract to improve and boost their journey.

Chung and her research team analyzed all sperm proteins in an effort to identify those which interacted with the CatSper maze. Eventually, they focused on one, known as EFCAB9, which performs as a kind of sensor, prompting various channels to open and close depending on what is happening within that particular environment.

“This molecule is a long-sought sensor for the CatSper channel, which is essential to fertilization, and explains how sperm respond to physiological cues,” Chung said.

Chung went on to say that EFCAB9 appears to play a double role in managing the activity as well as the layout of channels on a sperm’s tail, “which help regulate sperm motility towards the egg”.

Piecing together the journey

Prior studies have determined connections between mutations in the CatSper genes and male infertility. A November 2010 study review published in the European Journal of Human Genetics included an emphasis on ways in which the CatSper channel could be employed as a target area for a male contraceptive.

A 2009 study, also published in the journal Cell, explored the issue of human male infertility as the result of mutations in a particular CatSper channel protein. The researchers noted that the results indicate that this particular gene is “essential for normal male fertility in humans”.

And a 2013 study, published in the Proceedings of the National Academy of the Sciences (PNAS), detailed results which “unambiguously establish an important role of CatSper channel in human sperm nongenomic progesterone”, showing that the molecular mechanism that activates the gene happens fairly early in sperm development.

In the most recent study from Yale, Chung and the research team focus more on how a non-hormonal contraceptive might be developed that would cut down on side-effects in both women and men. The possibility also exists that further study of this important molecule will one day enhance fertility treatments.

With new and vital discoveries about fertility being made practically every day, men have some very important choices to make: Wait until a discovery address their particular needs in terms of boosting or safeguarding their fertility, and then decide to proactively store assets; or, to make the latter decision first, confident in the knowledge that as new discoveries continue to be made, they can revisit that choice again and again.

The Legacy man will no doubt “store and watch”, in order to take advantage of future treatments while continuing to safeguard his assets.