Fascinating Aspects of Glycobiology—Part 8 (Fertilization)

Larry A. Law

In the creation of life, sperm and ovum get together and connect via glycolipids and new life begins. It's like a key turning the lock. The ovum's membrane (glycocalyx) unlocks to allow a foreign cell to penetrate the ovum. Cells are very adverse to letting this type of thing happen. They are designed to protect what is inside from what is outside. Only the right key can unlock the door. This is especially true when it is something coming from a completely different human body! The process of pregnancy is really a miracle and an exception to what is normally permitted in the human body. 

A Key to Fit the Lock

Fertilization in pregnancy is a multi-step process (see picture above). In 2011, researchers identified the sugar receptor located on the female ovum which is recognized by the male sperm. They call the receptor Sialyl-LewisX (sLeX). It is a tetra-saccharide carbohydrate which means it is composed of four sugars—a special combination of sialic acid, fucose, galactose, and n-acetyl glucosamine (four of the eight glycobiology sugars). sLeX allows a male sperm cell to identify, attach, and fertilize a female egg. For fertilization to occur, human sperm must bind to the zona pellucida (ZP) which is the semitransparent shell covering the human egg (the jelly coat in the picture at the top of this blog article). The ZP has a forest of four types of glycolipids (ZP1-4)—see picture below. The sperm must bind to one of the glycolipids before it can fuse with the egg and release its DNA contents inside the ovum. It is interesting how once a sperm penetrates the ovum glycocalyx, all the other glycolipids lock down and no other sperm are allowed to bind (except in the relatively rare case of twins and triplets!). But the general rule is one sperm, one ovum, and one baby. 

Birth Control Measures

The ability of monosaccharides to effectively block sperm binding has been demonstrated in a number of species including humans. Scientists discovered "that L-fucose was the only sugar interfering with binding; other glycobiology sugars tested, including D-fucose, were proved to be completely ineffective." I mention this because it is a great example of how precise the body's reaction is to these sugars. The "L" stands for levo and the "D" stands for dextro (left and right in Latin). L-fucose means the fucose molecule is merely the flipped transposition of the D-fucose molecule (all the atoms remain the same, but the orientation is mirrored). But this reflection causes an entirely different reaction within the body! L-fucose prevents binding by the sperm and D-fucose does not. These sugars govern life from inception to death and all of the incredible biological processes in between. Geometry matters to the body! The picture below is a depiction of sperm trying to be the first to bind to the egg's glycoprotein and fertilize the ovum.