The remarkable journey of the sperm to the egg. (a) After intercourse, sperm enter the cervical mucus (1), where they begin capacitation. During passage to the uterus (2), the sperm induce a host reaction. Leukocytes, which outnumber the sperm 100:1, engulf normal and abnormal spermatozoa. In humans only one in 14,000,000 ejaculated human sperm reach the oviduct. Experiments in non-human mammals have shown that the oviduct (particularly the isthmus, where the duct is narrowest) (3) acts as a sperm store, potentially involving intimate contact between the sperm and the epithelial surface. Fertilization occurs in the oviduct (4). (b) In vitro experiments suggest that intracellular Ca2+ is low in the sperm that are attached to the isthmus epithelium (dark blue), and that this maintains their longevity and function. Before ovulation, the sperm detach, possibly as a result of the expression of hyperactivated motility. Detached cells (red) have higher intracellular Ca2+ levels and more vigorous motility and find the egg by responding to chemotactic cues (not yet identified in humans). (c) When the sperm reach the egg, hyperactivation enables penetration of the surrounding layer of cumulus cells (light blue) embedded in matrix (yellow) and the sperm attaches to the zona pellucida (5). Upon attachment the sperm undergoes the acrosome reaction, in response to binding of the zona pellucida (6), which, combined with hyperactivated motility, permits penetration of the zona (7) and fusion with the egg membrane (oolemma) (8). Adapted from .