The acrosomal reaction normally takes place in the ampulla of the fallopian tube (site of fertilization) when the sperm penetrates the secondary oocyte. A few events precede the actual acrosome reaction. The sperm cell acquires a "hyperactive motility pattern" by which its flagellum produces vigorous whip-like movements that propel the sperm through the cervical canal and uterine cavity, until it reaches the isthmus of the fallopian tube. The sperm approaches the ovum in the ampulla of the fallopian tube with the help of various mechanisms, including chemotaxis. Glycoproteins on the outer surface of the sperm then bind with glycoproteins on the zona pellucida of the ovum.
The first stage is the penetration of corona radiata, by releasing hyaluronidase from the acrosome to digest cumulus cells surrounding the oocyte and exposing acrosin attached to the inner membrane of the sperm. The cumulus cells are embedded in a gel-like substance made primarily of hyaluronic acid, and developed in the ovary with the egg and support it as it grows. After reaching the zona pellucida the actual acrosome reaction begins.
Acrosin digests the zona pellucida and membrane of the oocyte. Part of the sperm's cell membrane then fuses with the egg cell's membrane, and the contents of the head sink into the egg. In the mouse it has been demonstrated that ZP3, one of the proteins that make up the zona pellucida, binds to a partner molecule (to the β1,4-galactosyl transferase receptors) on the sperm. This lock-and-key type mechanism is species-specific and prevents the sperm and egg of different species from fusing. The zona pellucida also releases Ca granules to prevent additional sperm from binding. There is some evidence that this binding is what triggers the acrosome to release the enzymes that allow the sperm to fuse with the egg. It is likely that a similar mechanism occurs in other mammals, but the diversity of zona proteins across species means that the relevant protein and receptor may differ.
Upon penetration, if all is occurring normally, the process of egg-activation occurs and the oocyte is said to have become activated. This is thought to be induced by a specific protein phospholipase c zeta. It undergoes its secondary meiotic division, and the two haploid nuclei (paternal and maternal) fuse to form a zygote. In order to prevent polyspermy and minimise the possibility of producing a triploid zygote, several changes to the egg's cell membranes renders them impenetrable shortly after the first sperm enters the egg.
The aforementioned process describes the physiologically relevant events. One should however bear in mind that a certain percentage of sperm cells will undergo a spontaneous acrosome reaction without the presence of the ovum. Those cells are not able to fertilise the egg, even if they do reach it later. Other cells will spontaneously shed their acrosome during the process of apoptosis/necrosis.