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| Sperm-Egg Binding Interactions in Humans and Other Mammalian Models |
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| Every human being initially begins when a single human sperm binds to the egg and fuses with it to form a fertilized egg. This initial binding event seems to be extremely straightforward and should therefore be easily understood. Remarkably, while there is much known about how sperm-egg binding occurs in lower species like sea urchins, how this interaction occurs in humans and other mammals remains an enigma. There are many investigative groups across the globe that are trying to understand precisely how this binding event occurs. |
Understanding this interaction at the molecular level would certainly be beneficial to our society. A major advantage is related to the development of topical contraceptive foams and jellies. Today almost all agents of this type employ chemicals that kill sperm known as spermicides. The active ingredient in most spermicides is nonoxynol-9 (N-9). The problem with N-9 is that it actually increases a woman’s chance that she will become infected with HIV if she has intercourse with an HIV positive male. So beneficial contraceptive agents are needed hat specifically target a crucial sperm function necessary for fertilization, like binding to eggs. There could also be benefits in the fertility clinic. Some men are either infertile or subfertile because their sperm display deficient binding to eggs. If males with this problem could be routinely diagnosed, then measures could be taken to increase the chance that their female partners would become pregnant. |
In our laboratory, sperm binding to the egg has been investigated in the mouse and the human model systems. But certainly the most insightful studies have been performed using the mouse model. The reason why is because many more eggs can be obtained from mice, and sperm can also be easily harvested from males. However, even in the mouse the number of eggs is far less than optimal. Therefore our group is employing a very unusual system to investigate mouse sperm-egg binding. As shown in the photo on the right, mouse sperm also undergo very tight binding to rabbit red blood cells (also known as erythrocytes) to form clumps that are composed of both cell types. Sperm and eggs are usually referred to as germ cells, and other cells in the body are known as somatic cells. Therefore our model for this binding interaction is referred to as a “sperm-somatic cell adhesion system”. |
So how do mouse sperm bind to these rabbit erythrocytes? Data obtained in many different animal models suggest that sperm have proteins on their surface that bind to eggs. |
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| Scientists refer to these proteins as “egg binding proteins” (EBPs). Results obtained in lower animal models suggest that EBPs recognize sugars presented on the surface of the eggs and bind to them. These sugars are specifically attached to proteins that coat the egg surface. Sperm binding to the egg occurs at the microscopic level when sufficient numbers of these interactions between EBPs and these specific sugars occur at the molecular level. Our data indicate that mouse EBPs on sperm also bind to sugars that coat rabbit erythrocytes. In collaboration with Dr. Anne Dell at Imperial College London and her group (link to Anne Dell is http://www3.imperial.ac.uk/people/a.dell), we have recently determined that the sugars presented on eggs and those on these erythrocytes are not the same, but they do share some common structural features. So we can use this model system to investigate mouse sperm-egg binding. Hopefully in the near future our group will be able to determine exactly how initial sperm-egg binding occurs in the mouse. This information could then be employed to determine how sperm-egg binding occurs in humans, because there are overlaps in gene sequences between the mouse and the human in many types of proteins |
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