24 August 2021

Contraceptive antibodies

Antisperm antibodies reduced the number of motile spermatozoa by 99 percent in vivo

Anastasia Kuznetsova-Fantoni, N+1

American biologists have developed antibodies against spermatozoa, which can become an alternative to existing contraceptives. Antibodies delivered to the sheep's vagina along with the ejaculate reduced the number of motile sperm by 99 percent. In future experiments, scientists will have to find out how well antisperm antibodies prevent pregnancy. The study was published in Science Translational Medicine (Shrestha et al., Engineering sperm-binding IgG antibodies for the development of an effective nonhormonal female contraception).

Modern methods of contraception, although they offer reliable protection against unwanted pregnancy, have their drawbacks. For example, hormonal contraceptives have many side effects, including menstrual cycle changes, nausea, migraines, depression. Some women cannot take contraceptives containing estrogens because of the increased risk of thrombosis.

In nature, there is another mechanism of contraception: some women produce antibodies to sperm. Such antibodies, with a high concentration of spermatozoa, glue them into clusters and prevent penetration through the vaginal mucus. At a lower concentration of spermatozoa, antibodies contribute to the formation of complexes of spermatozoa with mucin fibers. Previously, these antibodies were used to create contraceptive vaccines, but studies have reached a dead end, as they could not guarantee the subsequent restoration of fertility.

American scientists led by Samuel K. Lai from The University of North Carolina has developed antisperm antibodies that are injected locally into the vagina. To increase the stability of such antibodies, they attached antigen binding sites to immunoglobulins G (previously, less stable IgMs were used in experiments). The antibodies target the CD52 antigen with an attached glycan. This form of CD52 is located only on the surface of the sperm cells of men and chimpanzees, and is not found in the body of women.

In order to test the antibodies in action, biologists injected 33 micrograms of antisperm antibodies into the sheep's vagina, and then injected human sperm, which was donated by volunteers. Previously, the total number of spermatozoa and the number of mobile forms were measured in it. Two minutes later, the liquid contents of the vagina were collected from the sheep, and the number of progressively mobile spermatozoa was counted under a microscope. These are the spermatozoa that move in a straight line and have the greatest chance of reaching the egg.

After antibody treatment, the number of progressively motile spermatozoa decreased by 99 percent. A man's normal ejaculate contains more than 32 percent of progressively motile spermatozoa. This means that such forms should have remained about 0.3 percent of the total sperm volume.

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Neutralizing ability of antisperm antibodies (green and blue columns) and IgG compared to saline (from the article by Shrestha et al.).

The authors of the work report that they have not yet looked at how effectively the antibodies prevent pregnancy, since the antigen they target is carried only by human and chimpanzee spermatozoa. Experiments on chimpanzees are banned in the United States, so scientists will have to decide how to test the antibodies further.

Andrologists have recently sounded the alarm: in a meta-analysis, they found that the number of spermatozoa in the sperm of men from developed countries fell by almost 60 percent. However, researchers from Harvard criticized the study of colleagues. They believe that the number of spermatozoa fluctuates both in individuals and in the population as a whole, and this indicator cannot be used to judge a decrease in fertility.

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