A discovery that inhibits the usual transition of sperm from a thick gel to a liquid holds promise for the development of a new non-hormonal, over-the-counter contraception method. A study lead by Washington State University discovered that inhibiting prostate-specific antigen in human ejaculate samples enabled the sperm to remain in its thick gel shape, retaining the majority of the sperm. Normally, the sperm will liquefy and swim through the female reproductive system to fertilize an ovum or egg. The discovery, which can halt the process, was published in the journal Biology of Reproduction.
“Our objective is to turn this into an easily accessible female contraceptive that would be offered on-demand, meaning women could go buy it off the shelf,” said senior author Joy Winuthayanon, associate professor and director of WSU’s Center for Reproductive Biology. “It might be used in conjunction with a condom to drastically reduce failure rates.”
Currently, the failure rate of over-the-counter contraceptives such as condoms and spermicides ranges from 13% to 21%, according to the study’s authors. Hormonal-based contraceptives, such as IUDs and birth control pills, have lower failure rates, but they can have side effects and are not always easily available or affordable, which may be one reason why the global unintended pregnancy rate is currently 48 percent, according to recent global health research.
Our goal is to turn this into an easily accessible female contraceptive that would be offered on-demand, meaning women could go buy it off the shelf. It might be used in conjunction with a condom to drastically reduce failure rates.
Prof. Joy Winuthayanon
The WSU team has been working on this contraceptive strategy since 2015, when it was revealed that some of the female mice in a previous reproductive study were unable to become pregnant; upon further investigation, the researchers discovered that the male’s semen was remaining in solid-state. The researchers subsequently attempted to deliberately block the sperm liquefication process in mice, and using a non-specific protease inhibitor called AEBSF, they were able to disrupt sperm motility and lower fertility in mice, as detailed in an earlier Biology of Reproduction publication.
The current study’s research team attempted to adapt those findings to human samples. They discovered that AEBSF had a contraceptive effect, but it was unclear if this was related to toxicity. The researchers next utilized an antibody to specifically target the prostate-specific antigen, or PSA, in human sperm. They picked PSA as the principal active protein in liquefication because it is released in significant quantities from the prostate gland, which is present in humans but not in mice.
Typically, following ejaculation, the PSA works on the gel-forming proteins known as Mongolians, according to first author Prashanth Anamthathmakula, who worked on the experiment as a WSU post-doctoral fellow.
“The semenogelins form a gel-like network with a thin protein mesh that catches the sperm. The PSA cleaves the mesh, allowing the sperm to escape “Anamthathmakula, who is now a senior research scientist at the University of Missouri-Kansas City, explained this. “We demonstrated that we could stop such liquefaction using a PSA inhibitor, an antibody.”
The next objective is to find more targeted small molecule inhibitors that would effectively prevent PSA from liquefying sperm without causing any negative side effects. Current spermicides have been proven to reduce natural vaginal barriers to sexually transmitted diseases such as HIV, according to the study. This advancement could avoid that type of toxicity by targeting the liquefaction process of the semen itself, but additional research is needed.
“It’s a bit of a protracted procedure since we don’t want off-target consequences,” Winuthayanon explained. “If we are going to develop this into a contraceptive product, it may be something that women will use frequently, so we want something that is safe and has no unforeseen consequences.”
“Our goal is to turn this into an easily accessible female contraceptive that would be offered on-demand, meaning women could go buy it off the shelf,” said Assoc. Prof. Joy Winuthayanon, senior author of a study on the topic. “It might be used in conjunction with a condom to drastically reduce failure rates.”
