Egg meets sperm

Although it is happening every hour of every day, all over the world, the story of egg meeting sperm is still a tale worth telling. Millions of candidates set off on a long and perilous journey with a single target at the end, and if the candidates reach their target, something completely unique is created. But before we get to the end, let’s take a closer look at the journey.

Zoom in on the egg (top) and sperm (bottom):

Hundreds of millions of sperm vie for a single egg cell. The sperm cells are streamlined in design for this purpose: a long tail to help them move, lots of mitochondria to power that movement, genetic information to pass on, and enzymatic proteins to get into the egg cell. The proteins are stored in a cap at the front of the sperm known as an acrosome - this is the part that first contacts the egg. The tail is called a flagellum, and it uses the energy made by the mitochondria to move the sperm forward. Flagella use a lot of energy, so they’re kept dormant until sperm enter the vagina. Sperm are haploid; they contain one set of 23 chromosomes. They are created by the cellular division process known as meiosis, which creates 4 sperm from a single germ cell. They’re also very small, only about 50μm long. Sperm are ejaculated in semen, a basic fluid with a pH of about 7.4.

The sperm's target is the egg. Since it is so much bigger than sperm, the egg is the source of cytosol and organelles, particularly mitochondria, for the future zygote. Unlike sperm, the egg has not completed meiosis - it’s stuck in the Metaphase II stage of division. This means that the egg is haploid but with sister chromatids still attached to each other. Also unlike sperm, the meiotic division to create eggs, oogenesis, only makes one viable egg. The egg is covered in a thick outer coating known as the zona pellucida, a layer of carbohydrate-covered proteins that surrounds the plasma membrane. The zona pellucida helps protect the egg and is responsible for mediating the initial meeting of sperm and egg. Cortical granules filled with enzymes line the inside of the cell membrane and help make sure that only one sperm can fertilize the egg.

Egg and sperm travel in opposite directions to meet in (most often) the fallopian tubes. During ovulation, ovaries release an egg into one of the fallopian tubes, and the egg proceeds down the tube toward the uterus, which is being prepared for possible implantation. Part of this preparation involves elevated levels of estrogen and luteinizing hormone (LH). LH triggers the ovaries to release the egg, while higher blood estrogen levels stimulate the vaginal membrane to secrete glycogen, which is then metabolized to lactate. This lowers vaginal pH (to as low as 3.8), creating an acidic environment hostile to pathogens (like the ones that cause sexually transmitted infections). However, this environment can also be toxic to sperm, though the semen (a basic fluid) can buffer the vaginal acidity to preserve sperm cells. As the semen mixes with the vaginal secretions, the pH settles at a point that is not harmful for sperm, and this new environment is the trigger to activate sperm flagella and increase sperms’ motility.

Only about 1 in 1 million sperm that are ejaculated into the vagina will reach the site of fertilization. Estrogen also relaxes the cervix, causes cervical mucus to become watery and more alkaline, and stimulates uterine contractions – all of which help sperm penetrate and navigate the female reproductive system. Relaxing the cervix allows sperm to pass from the vagina into the uterus and reduces a potential physical barrier. Cervical mucus may prevent sperm from passing into the uterus, but during ovulation when the egg is released from the ovaries, the mucus gets thinner and lower in pH. These changes make the mucus a great transport medium for the sperm, and help the sperm continue traveling. The uterine contractions actually help to push sperm toward the correct fallopian tube (the one with the egg), and recent studies have suggested that these contractions are more responsible for sperm movement than the sperm’s own propulsion mechanisms!

As we can see, the progress of sperm is really influenced by where in the menstrual cycle the female is. The closer to ovulation, the easier it is for sperm to pass. Scientists think this may be to conserve energy and resources - if the female isn’t ovulating, then there’s no target for the sperm, so it makes more sense to focus on protection against pathogens. The vagina and uterus are very susceptible to infection, so the body has to balance on a fine line between protecting these areas and allowing sperm to come through.

Let’s assume that despite the perilous journey, some amount of sperm cells have indeed found the egg and are ready to begin their approach. It’s not smooth sailing just yet – there are still physical and chemical barriers to overcome. As the sperm approach the egg, they bind to the zona pellucida in a process known as sperm binding. This triggers the acrosome reaction, in which the enzymes of the acrosome are freed. These enzymes then begin to digest the zona pellucida and allow the sperm to tunnel toward the egg’s plasma membrane. When the sperm cell finally reaches the egg cell, the plasma membranes of the two cells fuse together and the sperm releases its genetic material into the egg. At this point, fertilization has occurred, but we’re not done yet!

Fusion also triggers the cortical reaction. When the sperm and egg fuse it triggers a release of calcium ions, which cause the cortical granules inside the egg to fuse with the plasma membrane. As they fuse, these granules release their contents outside of the cell, toward the remains of the zona pellucida. The enzymes of the cortical granules further digest the zona pellucida, making it unable to bind more sperm, while other molecules found in the granules create a new protective layer around the fertilized egg. By creating a new barrier and destroying the initial interface between sperm and egg, the cortical reaction prevents polyspermy, or the fertilization of a single egg by multiple sperm. It’s like entering a hidden temple, but on the way, you set off hidden booby traps that make it impossible to ever enter again. Other sperm reaching the egg now are just shunted away.

Copper intrauterine devices, or IUDs take advantage of sperm cell properties to prevent fertilization. The copper released by these contraceptives is a natural spermicide, and ovicide, though it more strongly affects sperm. Studies have shown that copper ions reduce sperm’s motility, ability to trigger the acrosomal reaction, and general viability. Though the devices release less copper than what could be found in our diets, the copper build-up in the mucous lining of the cervix and uterine is enough to halt the movement of sperm. IUDs in general also trigger a mild inflammatory reaction that brings in immune cells that make it even harder for the sperm to complete their journey. Recently, some studies have even found that copper IUDs can affect the way the uterus contracts, sending sperm in the wrong direction! Thus, IUDs prevent the sperm and egg from ever meeting - inhibiting fertilization.