Human fertilization

Fertilization in humans happens when a sperm cell and an egg cell combine, usually in the ampulla section of the fallopian tube. This event creates a fertilized egg, called a zygote, which then starts embryonic development. The basic mechanics of human fertilization were worked out by scientists in the 1800s.

The process typically begins with ejaculation during sex, followed by ovulation, and ends with fertilization. But there are other possibilities, such as artificial insemination, in vitro fertilization, ejaculation outside the body without intercourse, or sex that happens just after ovulation. When a sperm meets the secondary oocyte, its acrosome releases enzymes that let it drill through the egg’s outer shell, the zona pellucida.

The sperm’s plasma then fuses with the egg’s plasma membrane, and their nuclei merge. This causes the sperm head to detach from its tail as the egg moves through the fallopian tube toward the uterus. In vitro fertilization (IVF) is a method where eggs are fertilized by sperm outside the body, in a lab dish.

History

In ancient times, fertilization was not understood. Hippocrates thought the embryo came from male semen plus a female factor. Aristotle, following the preformationist Pythagoras, believed only male semen produced an embryo, with the female merely providing a place for it to grow.

Aristotle also argued that form and function appear gradually, a concept he called epigenesis. In 1651, William Harvey rejected Aristotle’s idea that menstrual blood helped form a fetus, stating instead that female eggs somehow become a fetus after intercourse. Sperm cells were first seen in 1677 by Antonie van Leeuwenhoek, who thought this proved Aristotle right.

Some observers even believed they could see a tiny, fully formed human body inside a sperm’s head. The human egg was first observed in 1827 by Karl Ernst von Baer. It wasn’t until 1876 that Oscar Hertwig showed fertilization actually results from the fusion of an egg and a sperm.

A common way to describe fertilization is as a race where sperm rush to meet the egg. Another metaphor is that of two halves coming together to make a whole.

Ampulla

Fertilization takes place in the ampulla of the fallopian tube, the curved section near the ovary. Capacitated sperm, swimming at 1 to 3 mm per minute, are attracted to progesterone released by the cumulus cells around the oocyte.

Progesterone binds to the CatSper receptor on the sperm’s membrane, raising calcium levels inside the sperm and causing hyperactive movement. The sperm swim toward higher progesterone concentrations, guiding them to the oocyte. Only about 200 out of 200 million sperm actually reach the ampulla.

Sperm preparation

Freshly ejaculated sperm cannot fertilize well, so they must first undergo capacitation in the female reproductive tract. This process increases their motility and hyperpolarizes their membrane, preparing them for the acrosome reaction—the enzymatic breakdown of the egg’s tough outer layer, the zona pellucida.

Corona radiata

The sperm first binds through the corona radiata, a layer of follicle cells outside the secondary oocyte. The corona radiata releases chemicals that attract sperm in the fallopian tube to the oocyte. This layer sits above the zona pellucida, a glycoprotein membrane surrounding the oocyte.

Where a sperm is about to pierce, the ooplasm (yolk) is pulled out into a cone-shaped bump called the cone of attraction or reception cone. Once the sperm enters, the outer part of the yolk changes into the perivitelline membrane, which blocks other sperm from entering. After binding to the corona radiata, the sperm reaches the zona pellucida. A glycoprotein called ZP3 on the zona pellucida binds to a receptor on the sperm head.

This binding triggers the acrosome to burst, releasing enzymes that help the sperm drill through the thick zona pellucida to reach the egg’s cell membrane. Some sperm release their acrosome too early on the egg’s surface, which actually helps other sperm get through. Since mature haploid sperm share about 50% of their genome on average, this premature acrosome reaction can aid fertilization by a related sperm—a form of kin selection. Studies also show the egg is not passive; it undergoes changes that help the interaction.

After the sperm enters the oocyte’s cytoplasm, its tail and outer coating break down. The fusion of sperm and oocyte membranes triggers the cortical reaction.

Cortical granules inside the secondary oocyte fuse with the cell’s plasma membrane, releasing enzymes by exocytosis onto the zona pellucida. These enzymes cause the glycoproteins in the zona pellucida to cross-link—specifically, ZP2 is hydrolyzed into ZP2f—making the whole matrix hard and impenetrable to other sperm. This prevents more than one sperm from fertilizing the egg.