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Tracing sperm in the natural gel of sperm might lead to novel contraceptive methods

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Summary: A finding that prevents semen from converting from a thick gel to a liquid might lead to the creation of a new kind of non-hormonal, over-the-counter contraception. Blocking a prostate-specific antigen in human ejaculate samples allowed the semen to stay in its thick gel form, retaining the bulk of the sperm, according to a recent study.

A breakthrough that prevents semen from converting from a thick gel to a liquid might lead to the creation of a new kind of non-hormonal, over-the-counter contraception.

Blocking prostate-specific-antigen in human ejaculate samples allowed the semen to stay in its thick gel form, retaining the bulk of the sperm, according to a study headed by Washington State University. Semen will normally liquefy, enabling sperm to flow through the female reproductive system and fertilize an ovum or egg. The research, which was published in the journal Biology of Reproduction, was able to interrupt that process.

Senior author Joy Winuthayanon, associate professor and head of WSU’s Center for Reproductive Biology, stated, “Our objective is to convert this into a readily accessible female contraception that would be offered on-demand, meaning women could go purchase it off the shelf.” “It might be used in conjunction with a condom to greatly reduce the failure rate.”

According to the study’s authors, over-the-counter contraceptives such as condoms and spermicides have a failure rate of 13 percent to 21%. Hormonal-based contraceptives, such as IUDs and birth control pills, have lower failure rates, but they can have side effects and aren’t always readily available or affordable, which could be one reason why, according to recent global health research, the unintended pregnancy rate is now at 48 percent worldwide.

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The WSU team has been working on this contraceptive strategy since 2015, when it was found by chance that certain female mice in a previous reproductive study were unable to conceive; following further investigation, the researchers discovered that the male’s semen remained solid. The researchers subsequently sought to interrupt the semen liquification process in mice on purpose, and they were able to impair sperm motility and diminish fertility in mice using a non-specific protease inhibitor called AEBSF, as detailed in an earlier Biology of Reproduction publication.

The researchers in this study wanted to explore whether they could apply the findings to human samples. They discovered that AEBSF had a contraceptive effect, although it was unclear if this was related to its toxicity or something else. The prostate-specific antigen, or PSA, in human sperm was then targeted with an antibody. PSA was chosen as the principal active protein in liquefication because it is released in significant amounts by the prostate gland, which is present in humans but not in mice.

PSA typically works on the gel-forming proteins known as semenogelins after ejaculation, 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 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, expressed his gratitude. “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 can effectively stop PSA from liquefying sperm without causing any negative side effects. Current spermicides have been demonstrated to reduce natural vaginal barriers to sexually transmitted infections including HIV, according to the study. This advancement might prevent that sort of toxicity by focusing on the semen’s liquefaction phase, but additional study is needed.

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“It’s a lengthy procedure since we don’t want any off-target consequences,” Winuthayanon said. “If we turn this into a contraceptive device, it may be something that women use often, therefore we want something that is safe and has no unexpected consequences,” says the researcher.

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