In this article, we discuss how a reduced level of CD9 can negatively impact the fertility of females by preventing the fusion between egg and sperm cells.
What is CD9?
CD9 is a glycoprotein that is expressed on the cell surface, mainly of white blood and epithelial cells, in a wide variety of tissues. By interacting with several other proteins, it is involved in signal transduction. CD9 plays a role in the regulation of the development, growth and motility of cells. For example, by forming complexes with other molecules, it can trigger the activation and aggregation of platelets. Apart from that, this transmembrane protein also assists in certain viral infections and enhances the fusion of muscle cells. It also mediates cell adhesion and migration. Accordingly, it has been shown that reduced CD9 levels increase the motility and the metastasis capabilities of tumor cells.
The role of CD9 in fertility
The protein is also expressed on the surface of oocytes, and as such, it is involved in the fusion of egg and sperm cells during fertilization. Keeping this crucial function in mind, it is not surprising that a deficiency of this molecule can have a negative impact on the fertility of females. This was shown in a scientific study in which mice were bred that did not carry the CD9 gene, making them effectively deficient in the protein. Only 50 to 60 percent of these deficient females were able to produce offspring. Those that did had smaller litters of two instead of eight young on average. In addition to that, it took a longer time before they became pregnant. There was also an increased mortality rate in the litters. On the other hand, heterozygous females in whom only one CD9 gene is present, instead of the two present in normal females, did not display any reduced fertility. Notably, apart from these fertility issues, CD9-deficient mice appeared completely healthy. This suggests that the protein’s functions in different tissues could be taken over by other molecules, therefore not causing any additional problems.
How does CD9 deficiency decrease fertility?
It was shown that every event, including ovulating and successful mating, occurred normally, up until when a sperm and egg cell were supposed to fuse. Oocytes did not complete their second meiotic division and several sperm cells could be observed attached to the egg cell and ready to fuse. In vitro fertilization experiments on oocytes that did express CD9, in which antibodies were added to block the protein, gave similar negative results. Also, a comparison between the in vitro fertilization of CD9-carrying and CD9-deficient oocytes confirmed that the deficiency of this glycoprotein is, in fact, the cause of the problem. In another study, it was shown that injecting exogenous CD9 mRNA in deficient oocytes could restore normal fertilization rates. By performing similar experiments, this time with the injection of mRNA of a different molecule called CD81, it was discovered that the latter could compensate for the lack of CD9 for more or less 50 percent.
Is CD9 responsible for fertility problems in humans?
Because these findings raised concerns about whether or not CD9 could be responsible for the inability of women to procreate, a new study was performed. Here, the corresponding genes of 86 women with unexplained fertility problems were examined and compared with those of 164 fertile women. Although there was a certain variation of the gene caused by mutations, none of these could possibly be responsible for blocking the fusion between egg and sperm cells. Consequently, it can be concluded that CD9 cannot be scientifically linked to female infertility in humans.
In summary, CD9 plays a pivotal role in mediating a crucial event in the conception of offspring, the fusion between egg and sperm cells. If this protein is absent, this fusion is blocked and procreation is, therefore, impossible. Within our human population, there is a normal variation of the CD9 gene. However, since none of the investigated mutations are in the specific region of the protein that is responsible for egg-sperm fusion, its function is not inhibited. Therefore, there is no scientific evidence that infertility problems in women are associated with CD9.