Hundreds of millions of sperm cells swim energetically towards a single egg cell. Only one will fertilize it, and all the others will reach the end of their lives. How does the egg cell ensure that indeed, only one sperm cell penetrates it?

From among the hundreds of millions of sperm cells  collectively journeying towards the egg cell, only a single one succeeds in its mission to fertilize it. Once the victorious sperm cell penetrates the egg cell, the egg seals itself off, preventing other sperm cells from entering. How is this achieved?

A sperm cell comprises two main parts: the head, which contains the genetic material, and the tail, responsible for propulsion. At the front of the sperm cell’s head are enzymes—proteins that catalyze chemical processes—that are capable of breaking down the egg cell’s protective layer. Moreover, inside the egg cell, there are reservoirs of similar enzymes, awaiting the sperm's arrival.

The egg cell is enveloped in a complex matrix of proteins that protects it from harm, analogous to a cotton wool padding. This sticky protein matrix not only safeguards the egg but also helps the sperm to latch on to the egg. The first sperm cell that manages to cross the network and reach the membrane of the egg wins the race and fertilizes it.

At this stage the sperm cells are positioned very close to the egg cell. The challenge lies in the fact that the same complex, adhesive network that grabs and holds the sperm close to the egg cell also hinders them from reaching the egg cell’s membrane and penetrating it. The sperm cell uses its enzymes to break down the network and pave its way through. Concurrently, the egg cell itself releases chemical substances that break down the network enveloping it. Thus, the sperm cells close to the egg cell membrane can get even closer, while sperm cells that have not yet  been caught in the mesh can no longer connect to it.

The problem is that the enzymes that break down the protein network work relatively slowly, and a few seconds pass until the breakdown process is complete. Furthermore, other sperm cells reach the egg cell membrane almost simultaneously. So how is the penetration of other rapid sperm cells prevented?

In reality, the egg cell is much, much, larger than the sperm cell. A schematic diagram of the structure of the two gametes | Illustration: ducu59us, Shutterstock


The Electric Egg

In sea urchins and many other marine animals, a rapid electrical process  is activated upon the first connection between the sperm and the egg cell; it blocks the way for other sperm cells to reach the egg cell until the enzymes complete the slower chemical process of breaking down the protein network.

Initially, the egg cell is charged with a positive electric charge, and the sperm cells are charged with a negative electric charge. These opposing electric charges are attracted to each other, and thus the egg cell attracts the sperm cells. The moment a sperm cell connects to the egg cell's proteins, a rapid process is activated in which the egg cell absorbs sodium ions, which are positively charged particles. When the positive sodium ions enter the egg cell, its external environment becomes more negatively charged, creating electrical repulsion between the egg cell and the approaching sperm cells, which are negatively charged.

This change occurs within less than three seconds, and the egg also reverts to its original state relatively quickly. Thus many species also employ the slow process of enzymatic breaking down of the branched protein network to ensure that no additional sperm cells enter the egg cell in the long term.



As soon as one sperm cell connects to the egg cell, no other sperm cells can enter. The moment of fertilization | Illustration: MARK GARLICK / SCIENCE PHOTO LIBRARY

Mammal Egg Cells

In mammals, including humans, there is an additional process that helps prevent additional sperm cells from entering the egg cell. It’s not completely understood in humans, but it is being studied in mice.

Each one of our body’s cells is enveloped by a fatty membrane called the cell membrane, which defines the cell and protects its contents. The process that helps prevent the entry of additional sperm cells to the egg cell involves the blocking of this membrane. For a sperm cell to enter the egg cell it must attach to a receptor - a specific protein on the egg cell’s membrane that can initiate the process of entry into the egg. The surface of sperm cells contains proteins that are compatible with these receptors, like a key to a lock. As soon as the first sperm cell connects to one of the receptors on the egg cell, the rest of the receptors disappear rapidly from its surface, and other sperm cells cannot enter. A study in mice identified the proteins involved in this process; the researchers named the receptor Juno, after the Roman goddess of protection of women, marriage, motherhood, and childbirth.

The researchers found that the genes encoding for the receptor on the egg cell surface and for the surface protein of the sperm cell, which binds to it, are present in all marsupials and mammals, including humans. In other words, the additional mechanism that prevents the entry of further sperm cells into the egg cell seems to be universally shared among mammals and is present also in humans,  involving the removal of the receptors from the cell surface of the egg cell. 

In rabbits, the membrane-blocking process is very effective, thus they barely need to break down the complex protein network. In contrast, in dogs and sheep the blocking of the membrane is less efficient, and the prevention of additional sperm cells from entering the egg cell is achieved almost exclusively through the breakdown of the protein network. Humans, as well as mice, rats, cats, pigs, and cows apparently use both processes: blocking the membrane and breaking down the protein network, to ensure that only a single sperm cell successfully fertilizes the egg.


Each group of organisms employ slightly different methods, but they all converge on the same goal: the fertilization of one egg cell by a single sperm cell. Sperm cells and an egg cell | Illustration: K.K.T. Madhusanka, Shutterstock


Connecting and Merging

Once the victorious sperm cell outcompetes all the others and binds to the proteins on the surface of the egg cell, their cell membranes come into contact and merge. The lipids constituting the egg cell membrane join with those of the sperm cell membrane, allowing the contents of the sperm cell, primarily its DNA, to enter the egg cells, resulting in fertilization. Both the egg cell and the sperm cell each contain a single copy of DNA. During fertilization, a new cell containing two copies of DNA, akin to most somatic cells, forms, and it can begin replicating and dividing.

In the rare event of a mishap, where two sperm cells manage to enter the egg cell,  problems typically arise during subsequent cell division, due to the unequal distribution of genetic material, resulting in cessation of early embryo development. In exceedingly rare cases, semi-identical twins may form. This phenomenon has been reported only twice to date: once in 2007, and again in 2019. In such cases, the half-identical twins share identical DNA from their mother, who contributed a single egg cell, but they share only part of the paternal DNA, as each twin receives genetic material from a different sperm cell.