4 Preparing for conception
4.5 Gamete production in women
It is time now to turn to the question of how female gametes – eggs – are made. There are substantial differences between sperm and eggs, and consequently their production pathways are very different.
Q Can you give one similarity in the production of eggs and sperm?
A Both are gametes, so must undergo meiosis to reduce the number of chromosomes by half.
In contrast to sperm, which contribute, along with a set of chromosomes, only a very small quantity of cytoplasm to the fertilized egg, the egg itself contributes a large amount of cytoplasm. Indeed, the egg is among the largest of human cells, being in the range of 90–1201μm (i.e. around one-tenth of a millimetre) in diameter – practically visible with the naked eye. As you will learn later, the growing embryo lives without the benefit of a placenta for the first two weeks of its life, so the egg's cytoplasm must supply many of its needs during this time (the rest can be obtained from the liquid in which it is bathed – see below). It is quite demanding for a cell to produce so much cytoplasm – making all those proteins, for example, is expensive in terms of energy and raw materials – so the developing egg is nourished by a group of ‘ladies-in-waiting’ called granulosa cells, which develop alongside the egg, and remain in close contact with it.
Egg production takes place in the ovary, which, unlike the testis, remains in the abdomen at 371°C. As with sperm production, there are three phases involved, but they are not sequential. Mitosis and meiosis occur as before, but the packaging part of the maturation phase is replaced by a growth phase which increases the amount of cytoplasm, and which occurs concurrently with a large part of the meiotic phase. Only one egg is ovulated each month, so that you might expect the whole development phase to take around a month to complete. You may therefore be surprised to learn that the process can take more than 50 years! This is because egg development begins before birth, in the first month of gestation in fact. The cells destined to become eggs begin their mitotic cycles then, and all the cells begin meiosis before birth. This means that at birth, a girl will have in her ovaries all the oocytes (pronounced ‘oh-oh-sites’ – partially matured eggs) that she will ever have. If these are destroyed, for example by exposure to radiation, the woman will be infertile. Unlike the situation with sperm, which die a few days after their completion, at this stage of development the oocytes remain alive, but enter a kind of suspended animation known as arrest. All will stay arrested until puberty, after which time some will be stimulated to carry on through meiosis. Although there are more than two million oocytes present at birth, only a few hundred will ever proceed to maturity (and fewer still will be fertilized). Nevertheless, after puberty a few are reactivated every day, resulting in a steady trickle of maturing oocytes, one of which will be released each month.
Each oocyte is enclosed in a follicle (small sac), whose cells, as we mentioned above, encourage its maturation and growth (see Figure 13). The oocytes are arrested at a very early stage of meiosis, at the time when the four chromatids (i.e. the two pairs of duplicated chromosomes) are in intimate contact with each other (see Figure 9c). They resume meiosis, but in an unusual way: at the end of the First division, half the chromosomes, but almost all the cytoplasm, go to one cell. The remaining chromosomes are discarded in a small bag on the outside of the large cell, called the first polar body, and are subsequently destroyed. The ‘big’ oocyte resumes meiosis, its chromosomes lining up at the equator for the second time, but the process is then arrested again. The oocyte is ovulated in this state. Meiosis is not reactivated until 2–3 hours after fertilization when, once again, one set of chromosomes is expelled in a polar body (the second) and lost. Thus, in contrast to male meiosis which results in four gametes, in women there is only one, which is relatively very large; Figure 14 shows the relative sizes of the egg and the polar bodies.
Figure 13, (a) Diagram of ovary to show the development of a follicle and the production of a mature oocyte. Maturation proceeds clockwise from the top left. One of the primordial (undeveloped) follicles is stimulated, and starts to grow. (b) Enlarged diagram showing the follicle containing the oocyte, a lot of fuid, and the granulosa cells which nourish the oocyte. Note that after ovulation the follicle itself develops into a structure called the corpus luteum, which plays a role in pregnancy.
Figure 14, Photograph of fertilized egg with two polar bodies. This photograph also shows the two sets of chromosomes present in a fertilized egg, one set derived from the mother and the other derived from the father. Because the sets of chromosomes do not constitute a proper nucleus, it is more accurate to refer to each as a pronucleus (plural: pronuclei). The polar bodies contain the other sets of chromosomes derived from the two cell divisions of the meiosis that produced the egg: they will eventually detach and degenerate.
The maturation of the oocyte is often called the follicular phase, as it occurs while the oocyte is within the follicle. It is characterized by a massive amount of protein synthesis in the oocyte, which loads up the cytoplasm with all the ‘goodies’ that a newly fertilized egg will need. The surrounding follicle cells also undergo mitosis to form a thick layer around the oocyte. They make a protective jelly coat, called the zona pellucida, between themselves and the oocyte, but maintain contact with it by means of long strands of cytoplasm which pass through the zona. All this happens spontaneously, without any hormonal infuences from the brain or elsewhere. However, towards the end of this first step, some of the follicle cells develop the ability to respond to FSH and LH, and this ability is crucial for the process to go further.
Because of the slow trickle of oocytes into the first phase of maturation, at any point in time there are always a few follicles which have reached the end of this first step. There are two possible fates for these follicles: either they will degenerate and die, or, if sufficient levels of LH and FSH are present, and the cells can respond to them, another round of mitosis will occur in the follicle cells, making the follicle bigger. At this stage, the oocyte itself does not increase in size, but the follicle enlarges even more because its cells begin to secrete a fuid which surrounds and cushions the oocyte (see Figure 13b). The follicle cells also start to make certain sex hormones, including testosterone and oestrogen. As with the testis, the ovarian follicle does this in response to hormonal cues from the brain. The oestrogen is important: it causes even more of the follicle cells to become sensitive to LH, and this, in its turn, is vital for further maturation. Once again, the increase in sensitivity must coincide with an increase in levels of LH, otherwise the follicle will degenerate. If the timing is good, then the oocyte can enter into the final maturation phase, the pre-ovulatory phase. The pre-ovulatory phase coincides with the progress of the oocyte through the first meiotic division, and it results in the oocyte being ovulated, i.e. released from the surface of the follicle, together with the first polar body (Figure 13a). Once this occurs, the follicle continues to secrete hormones, but different ones, and in different amounts: it becomes a corpus luteum, making progestogen, not oestrogen, in preparation for a possible pregnancy.
Although both the resumption of meiosis and cytoplasmic maturation are stimulated by an increase in local levels of LH, the oocyte itself is not sensitive to LH: the effect comes via the LH-sensitive follicle cells. By the time of ovulation the oocyte is at the surface of the follicle, separated from the outside world by only a thin layer of cells. Increased fuid pressure within the follicle causes it to pop, and the egg, still surrounded by some granulosa cells but no longer firmly attached to them, is ejected. It enters the Fallopian tube (see Figure 5), where it is wafted gently downwards by the fimbriae lining the tube. Fertilization can take place in the Fallopian tube if sperm are present there.
Q Within how many days must intercourse have occurred for there to be fertile sperm in the Fallopian tubes?
A Within five days (Section 3).