MoBio Fertilization Chapter 8

Fertilization refers to the fusion of a sperm with an egg. In the somatic cells of humans, the normal diploid number of chromosomes is 46 (23 pairs), but a germ cell (sperm or egg) contains only 23 chromosomes. Fusion between the sperm and egg restores the number of chromosomes to be the same as in a somatic cell.

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.

Acrosome Reaction

The mature oocyte (ovum) is surrounded by a protective coat of non-cellular material called zona pellucida. To fertilize the egg, the sperm cell must bind to and penetrate the zona pellucida, fuse with the egg's cell membrane and enter its cytoplasm. The process of penetrating through the zona pellucida is called acrosome reaction. The acrosome is an organelle located at the anterior half of the head of a sperm cell.

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Figure 2-1. Acrosome reaction on a Sea Urchin cell. (Source: Wikipedia).

Activation of the Egg

Ca2+ ions play a central role in the amazing development from a single cell to an embryo, because many enzymes are calcium-dependent. In addition to chromosomes, the major ingredient in a sperm is an enzyme that can initiate the release of Ca2+ 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 can move 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-ζ (zeta) from the sperm cytosol. It has been demonstrated that injection of the enzyme PLC-ζ into the human egg can induce calcium waves as seen in normal fertilization.

Resumption of cell cycle

Prior to fertilization, the egg is arrested at the 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, the daughter cells should have the same DNA sequences. Then, how can a fertilized egg produce 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.