5.1 How fertilization happens
Now that we have dealt with the basic biology, we can resume and give more detail to our story, and return to where we left it: fully mature, strongly swimming sperm have been deposited in the vagina, and will begin their race to the newly ovulated egg.
Q Where do the sperm have to go to fertilize an egg?
A Through the cervix, up through the uterus, and into the Fallopian tubes (see Figure 5).
Immediately following ejaculation, the semen coagulates, which reduces loss from the vagina due to gravity. However, it soon liquefies again, and most of it leaks from the vagina, but within a minute or two of ejaculation some sperm have already swum through the cervix and entered the uterus. They may be helped on their way both by the wafting motion of cilia lining the entrance to the cervix, and also by muscular contractions of the woman's reproductive tract if she has experienced orgasm, but these are not required. It used to be thought that sperm do not swim purposefully up the reproductive tract: that their direction of swimming is completely random, and, indeed, changes frequently, and that sperm only get to the ‘right’ place by luck. However, it has recently been reported that sperm have a net tendency to swim up the Fallopian tube containing the recently ovulated egg, rather than the other tube. It is not clear how the sperm accomplish this, but it is possible that they are responding to subtle chemical signals. Whatever the mechanism turns out to be, the first hurdle is getting through the cervix.
Q Why is this difficult?
A The cervix is plugged with mucus. This is normally very viscous, but becomes thinner around the time of ovulation.
Of the many sperm ejaculated, only about 100 get through to the uterus. These then undergo a process called capacitation, the precise nature of which is not known, but is necessary to give them the capacity to fertilize an egg. The process can only occur in the uterus when it has been ‘primed’ by oestrogen (that is, at a particular point in the menstrual cycle), and takes several hours. Even after capacitation, sperm are still not fully able to fertilize: they require one final change, called activation. Activation involves changes to the membranes surrounding the sperm, including the one surrounding the acrosome. This develops holes, releasing from inside the acrosome an enzyme called hyaluronidase. Another change at activation is in the swimming properties of the sperm. Instead of the regular, wave-like beats used up to this stage, the tail starts to beat in a periodic, whiplash movement, propelling the sperm along in lurches. Activation must take place very close to the egg, as once it has occurred the sperm will not survive for long.
The sperm become activated in the Fallopian tube, where they will meet the moving egg, still surrounded by some follicle cells. The follicle cells are removed by the action of the hyaluronidase from the acrosome (by digestion of the polysaccharide material holding the cells together) and the sperm stick to the outside of the zona pellucida, as shown in Figure 16. Other enzymes from the acrosome (e.g. protein-digesting ones) produce a path through the zona, and the whiplash movement of the tails propels the sperm along their paths, leaving them in close proximity to the egg. The membrane of one of them fuses with that of the egg. This sperm stops all swimming movements immediately, and a change takes place in the egg membrane which effectively stops any other sperm from fusing with it. Enzymes are released from the egg's surface which alter the structure of the zona and prevent any further sperm from penetrating it. These events take place within a few minutes of fusion, and the chromosomes of the successful sperm begin to move into the egg cytoplasm. The final part of fertilization, taking longer but absolutely vital, is the egg's resumption of meiosis to get rid of the extra set of chromosomes. Two to three hours after fusion the second polar body is extruded, and the fertilized egg is left with one set of maternal chromosomes to complement the paternal set from the sperm. Although the two chromosome sets are independent to begin with, and so are called pronuclei (these can be seen in Figure 14), by the time of the first division of the fertilized egg the chromosomes have mingled and will all come to lie in the same equatorial plane. This would appear to mark the time at which the embryo becomes autonomous, but as you will see below, this is not necessarily the case. However, it is certainly a prerequisite for a new individual.
If the egg is old, i.e. was ovulated several hours before fertilization, the processes described above may not occur accurately.
Q Can you predict what sort of errors might occur?
A If more than one sperm fused with the egg, or if the second polar body was not extruded, there would be too many sets of chromosomes in the fertilized egg. This would produce abnormal embryos.