The egg

At ovulation, the egg is arrested in metaphase of the second meiotic division (Chapter 4). It is surrounded by a proteinaceous sphere called the zona pellucida. Those granulosa cells that adhered to the surface of the zona pellucida and were expelled with the egg from the ovary remain attached as the cumulus. Sperm that fertilize the egg must first negotiate these surrounding layers before they can penetrate the egg cell membrane. The oocyte will remain viable for at least 6–24 h once ovulated.

The sperm

With coitus, millions of sperm are deposited in the upper vagina. Most will never arrive at the site of fertilization. Abnormal sperm can rarely make this long trip successfully and even most of the healthy spermatozoa die along the way. The vast majority leak from the vagina upon liquification of the semen. Only a small proportion enters the cervix, where sperm will be found within minutes of coitus. Here they can survive within the epithelial crypts for hours. Sperm cannot traverse the cervix into the uterine cavity unless the cervical mucous is receptive. This typically occurs at midcycle when estrogen levels are high and progesterone is low. Estrogen softens the cervical stroma and makes cervical secretions thin and watery. Progesterone has opposite effects, a combination hostile to spermatozoa.

In the best of conditions, it takes 2–7 h for sperm to move through the uterus to the site of fertilization within the oviduct. Sperm transport results from self-propulsion, aided by the ciliary beating of cells within the uterine lining. Typically, only several hundred sperm reach the oviducts, where they will linger in a quiet state until ovulation occurs. After ovulation, these spermatozoa are reactivated and begin moving toward the egg. The signal that attracts the sperm to the egg is unknown. Human spermatozoa can survive for approximately of 24–48 h in the female reproductive tract.

Freshly ejaculated spermatozoa are not capable of fertilizing an egg. They acquire the ability to penetrate the cell layers surrounding the oocyte through a process known as capacitation. Although capacitation can be induced in vitro under the proper culture conditions, it occurs in vivo within the female reproductive tract. During capacitation, the glycoprotein coat that adheres to the spermatozoa cell membranes is initially removed, initiating changes in the surface charge of the sperm membrane and reorganization of that membrane. Capacitated sperm change their tail movements from regular undulating waves to whip-like, thrashing movements that propel the sperm forward. At the biochemical level, capacitated sperm acquire increased calcium sensitivity and elevated internal cAMP levels. Capacitation takes several hours both in vivo and in vitro.

Sperm capacitation allows for the acrosome reaction. In the absence of an acrosome reaction, a sperm is incapable of penetrating the zona pellucida. Contact of an intact, capacitated sperm with the zona pellucida of an egg allows interaction of a specific sperm cell surface glycoprotein, ZP3, with specific zona protein. These interactions are likely mediated by the sugars on sperm–egg binding proteins. ZP3-binding induces further calcium influx into the spermatozoa and intracellular cAMP levels rise. The acrosome swells, its outer membrane fuses with the sperm plasma membrane, and the enzymatic contents of the acrosome are released into the extracellular space surrounding the head of the sperm. This exposes the inner acrosomal membrane and another zona-binding protein, ZP2, to the oocyte zona. ZP2 binding holds sperm near the egg. Proteolytic enzymes released from the acrosome then facilitate penetration of the zona pellucida by the whiplashing sperm. Complete penetration of the zona takes about 15 minutes.