Fertilization

Prior to fertilization in humans and mice, the egg (oocyte) enlarges, divides by meiosis, and matures in its ovarian follicle until it reaches a stage of meiotic division called metaphase II. At this point, the follicle releases the oocyte into the oviduct, one of two tube-like structures that lead from the ovaries to the uterus. The mature oocyte, a haploid cell that contains half the normal number of chromosomes, is surrounded by a protective coat of noncellular material called the zona pellucida. For fertilization to occur, a haploid sperm cell must bind to and penetrate the zona pellucida, fuse with the cell membrane of the oocyte, enter the oocyte cytoplasm, and fuse its pronucleus with the oocyte pronucleus. Fusion of the sperm and egg pronuclei restores the number of chromosomes that is typical of a given species. In humans, the normal diploid number of chromosomes for all the cells of the body (somatic cells) is 46 (23 pairs of chromosomes). Mature sperm and egg cells (germ cells) in contrast, carry only 23 chromosomes, the haploid number.

In addition to the fusion of genetic material from sperm and egg, fertilization must also activate the egg to start development. The egg is activated by calcium ions originally stored in the endoplasmic reticulum of the egg.

Release of Ca²⁺ Ions

Ca²⁺ ions are released through IP₃-sensitive Ca²⁺ channels located on the membrane of endoplasmic reticulum. In the absence of IP₃ (inositol 1,4,5-trisphosphate), this type of Ca²⁺ channels are closed and the Ca²⁺ ions remain in the endoplasmic reticulum. Upon binding of IP₃ molecules, the Ca²⁺ channels open and the Ca²⁺ ions are released from the endoplasmic reticulum to the cytosol.

IP₃ can be generated by the enzyme phospholipase C (PLC) which splits a membrane phospholipid, PIP₂ (phosphatidyl-inositol 4,5-bisphosphate), into diacylglycerol (DAG) and IP₃. There are many types of PLC, each can be activated by different pathways. The PLC responsible for the release of Ca²⁺ ions in the egg is species-dependent. In mammals, it is the type PLC-z ( zeta) from the sperm cytosol. It has been demonstrated that injection of the enzyme PLC-z into the human egg can induce calcium waves as seen in normal fertilization.

Activation of the Egg

Upon the entry of the sperm, the egg is "awakened". A series of changes must be made to initiate the complex development. Ca²⁺ ions play a central role in the egg activation, because many enzymes are calcium-dependent.

To initiate development, an activated egg must (1) resume cell cycle, and (2) rearrange cytoplasmic materials.

Resumption of cell cycle

Prior to fertilization, the egg is arrested at metaphase II (MetII) of its meiotic division. The MetII arrest is maintained by high level of MPF (mitosis promoting factor), which consists of two components: Cyclin B and cyclin-dependent kinase. In the absence of Cyclin B, MPF is inactive. Ca²⁺ can stimulate the degradation of Cyclin B to resume the cell cycle.

Rearrangement of egg cytoplasm

After cell division (cleavage), the daughter cells should have the same DNA sequences. Then, how could a fertilized egg produces many types of cells? The earliest cell differentiation arises from rearrangement of the egg cytoplasm so that different segments contain different proteins and RNAs that regulate gene expression. Although the daughter cells have the same DNA sequences, but they may have different gene regulators, thereby possessing different characteristics.

References:

National Institute of Health, USA.
Mammalian egg activation: from Ca²⁺ spiking to cell cycle progression - Reproduction, 2005.