FERTILIZATION AND EARLY CLEAVAGE

Reff :  Katz: Comprehensive Gynecology, 5th ed.

         In most mammals, including humans, the egg is released from the ovary in the metaphase II stage. When the egg enters the fallopian tube, it is surrounded by a cumulus of granulosa cells (cumulus oophorus) and intimately surrounded by a clear zona pellucida. Within the zona pellucida are both the egg and the first polar body. Meanwhile, spermatozoa are transported through the cervical mucus and the uterus and into the fallopian tubes. During this transport period the sperm undergo two changes: capacitation and acrosome reaction. These changes activate enzyme systems within the sperm head and make it possible for the sperm to transgress the cumulus oophorus and the zona pellucida.

       The sperm are attracted to an egg through the process known as chemotaxis, which is related to capacitation of the sperm. The process is aided by the binding of progesterone to a surface receptor on the sperm. This allows an increase in intracellular calcium ion concentration, which increases sperm motility (chemokinesis). Once the sperm has passed the barrier of the zona pellucida, it attaches to the cell membrane of the egg and enters the cytoplasm. When the sperm enters the cytoplasm, intracytoplasmic structures, the coronal granules, arrange themselves in an orderly fashion around the outermost portion of the cytoplasm just beneath the cytoplasmic membrane, and the sperm head swells and gives rise to the male pronucleus. The egg completes its second meiotic division, casting off the second polar body to a position also beneath the zona pellucida. The female pronucleus swells as well. In most mammals the male pronucleus can be recognized as the larger of the two. The pronuclei, which contain the haploid sets of chromosomes of maternal and paternal origin, do not fuse in mammals. How-ever, the nuclear membranes surrounding them disappear, and the chromosomes contained within each membrane arrange themselves on the developing spindle of the first mitotic division. In this way the diploid complement of chromosomes is reestablished, completing the process of fertilization.

         Cell division (cleavage) then occurs, giving rise to the two-cell embryo. The first division takes about 20 hours to complete, and the actual phase of fertilization generally occurs in the ampulla of the fallopian tube. A significant number of fertilized ova do not complete cleavage for a number of reasons, including failure of appropriate chromosome arrangement on the spindle, specific gene defects that prevent the formation of the spindle, and environmental factors. Importantly, teratogens acting at this point are usually either completely destructive or cause little or no effect. Twinning may occur by the separation of the two cells produced by cleavage, each of which has the potential to develop into a separate embryo. Twinning may occur at any stage until the formation of the blastula, since each cell is totipotential. Both genetic and environmental factors are probably involved in the causation of twinning.