Sperm retention in natural sperm gel

The discovery, which blocks the normal transition of sperm from a thick gel to a liquid, promises the development of a new form of non-hormonal contraception that is available without a prescription.

A research team led by the University of Washington recently found that blocking prostate-specific antigen in human ejaculate samples causes sperm to remain as a thick gel, trapping most of the sperm. Usually the sperm is diluted, allowing the sperm to pass through the female reproductive system to fertilize the egg or ovum. The discovery is able to stop this process and is described in detail in the journal Biology of reproduction.

“Our goal is to develop it into an readily available female contraceptive that will be available on request, which means women can buy it off the shelf,” said senior author Joy Vinutayanon, associate professor and director of the WSU Center for Reproductive Biology. “It can be used in combination with a condom to significantly reduce the failure rate.”

Currently, over-the-counter contraceptives, such as condoms and spermicides, have an average of 13% to 21% of failures, the study authors noted. Hormonal contraceptives, such as IUDs and birth control pills, have lower failure rates, but they can have some side effects and are not always readily available or affordable, which may be one of the reasons why worldwide unintentional pregnancies currently stands at 48%, according to up-to-date global health research.

Human semen treated with AEBSF

Control sample of human semen (left) compared to the sample processed by AEBSF to block sperm dilution (right). Author: Washington State University

The WSU team has been working on this method of contraception since 2015 after it was accidentally discovered that some female mice in another reproductive study could not conceive; upon further investigation, the researchers found that the man’s semen remained solid. The researchers then tried to intentionally stop the process of liquefying sperm in mice, and using a nonspecific protease inhibitor called AEBSF, they were able to disrupt sperm movement and reduce fertility in mice by detailing their results in the study. before Biology of reproduction paper.

In the current study, the research team worked to see if they could translate these results into human samples. They found that AEBSF did have a contraceptive effect, but it was unclear whether it was simply because of its toxicity. They then used antibodies targeting prostate-specific antigen or PSA in human semen. They chose PSA because it is the major active protein in dilution and is secreted in large amounts from the prostate, which is present in humans but not in mice.

Typically, after ejaculation, PSA acts on gel-forming proteins called semenogenelines, explained first author Proshant Anamttmakula, who worked as a WSU doctor on the project.

“Semenogelins create a gel network with a thin network of proteins that traps sperm. PSA breaks down this network, and sperm becomes free, ”said Anamtmakula, who is now a senior fellow at the University of Missouri-Kansas City. “Using a PSA inhibitor, an antibody, we have shown that we can block this dilution.”

The next step is to identify more specific small molecule inhibitors that would effectively prevent the ability of PSA to dilute sperm without any harmful side effects. Researchers have noted that modern spermicides lower natural vaginal barriers against sexually transmitted diseases such as HIV. By targeting the process of liquefying the sperm itself, this progress can avoid this type of toxicity, but further research is needed.

“It’s a bit of a long process because we don’t want inappropriate effects,” Vinutayanon said. “If we’re going to develop this into contraceptives, it could be something that women will use often, so we want something safe and has no unintended effects.”

Reference: “Blocking the activity of serine protease prevents the degradation of semen gelin, which leads to hyperviscous sperm in humans” Proshanta Anamtmakula, Jeffrey Eriksson and Vipavi Vinutayanon, January 29, 2022, Biology of reproduction.
DOI: 10.1093 / biolre / ioac023

Funding: NIH / National Institute of Child Health and Human Development Eunice Kennedy Shriver Sperm retention in natural sperm gel

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