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Temporal course of the number of germ cells / follicles
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During the fetal period, the count of germ cells in the female organism is subject to large variations. These arise due to the fact that the phases of proliferation and decomposition of oocytes described below take place partially stepwise and partially in parallel.
Phase A:
Primordial germ cells grow, proliferate and become sheathed with coelomic epithelial cells. Gonadal cords arise; 6th to 8th week.
Phase B:
Spurt of growth: cellular clones of the oogonia are formed, whereby the cells remain connected with each other through cellular bridges; 9th to the 22nd week.
Phase C:
The oogonia become primary oocytes that enter the prophase of the first meiosis; 12th to the 25th week.
Phase D:
The primary oocytes become arrested in the dictyotene stage of the prophase: the primordial follicles are engendered; 16th to the 29th week.
Phase E:
At around the 14th week a quantitatively increased decline in the number of germ cells commences as well as atresia in all of the follicle stages.
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Commentary
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Up to the 22nd week of pregnancy, the primordial germ cells multiply along with the resulting oogonia by mitosis. The maximum number of germ cells (7 million), found in an ovary, is reached already in the 20th week due to the concomitant massive degeneration of germ cells that begins in the 14th week. At the time of birth only about 2 million germ cells are still present in the ovary.
The very first primary oocytes enter the prophase in the 12th week. The passage through the various stages, up to the arresting of further development, takes approximately 4 weeks and is accompanied by a restructuring of the epithelial covering (coelomic epithelium --> follicular epithelium), so that the first primordial follicle with the primary oocyte, arrested in the dictyotene stage, appears roughly 4 weeks later in the 16th week. Today it is assumed that the generation of the primordial follicles is complete by the time of birth.
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The result of these processes on the count of germ cells is portrayed in the following diagram.
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| Fig. 22 - Development of the germ cell count in the various phases |
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Fig. 22
The upper plot shows the time span in which specific processes operate on the germ cells.
The lower plot shows the age-dependent changes of the total number of oogonia (or oocytes) and follicles in a single ovary.
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Atresia - the customary fate of a follicle
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The normal, common fate of a follicle or female germ cell is known as atresia - ovulation represents an exceptional destiny.
The above plot shows clearly how the number of germ cells decreases from the 20th week in order that they are all gone by about 50 years of age. Even though the decrease actually proceeds continuously, three moments in the life of a woman are apparent in which this takes place more rapidly. The largest decrease occurs in the 20th week after the maximum number of 7 million germ cells (per ovary) is reached, thus still in the fetal period. Immediately following birth a further, short period of accelerated decline happens. The third, temporally longest period, of increased decline takes place during puberty.
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| One terms the decline or the regression of follicles of each stage at every time in the life of a woman follicular atresia. These follicles do not ovulate and the name is derived from that fact. Follicle atresia occurs more intensely, though, at certain moments (fetal period, early postnatal, begin of the menarche). |
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Explanations for the onset of heightened atresia are:
a) in the 14th week:
Already during the meiotic prophase, mainly in the pachytene stage (lasts the longest, around 3 weeks), the cells are especially susceptible and succumb. With the formation of the primordial follicle in the 16th week the follicular atresia also begins as an additional reason for the decline in the number of germ cells. Both processes together cause the germ cell count to shrink to a third (somewhat over 2 million / ovary) of the maximum number.
b) postnatal:
During the fetal period sex hormones are produced in the placenta. This results in a high estrogen level in the blood of the mother and of the fetus. This gives rise to a considerable maturation of the primordial follicles up to the tertiary follicle phase in the female fetus. When the sex hormone level in the fetus sinks after birth all of the previously matured follicles become atretic (a slight withdrawal bleeding can even occur in the newly born from the 5th to the 10th day). Per ovary there are then less than 2 million germ cells present afterwards.
c) during puberty:
With the onset of puberty (at around 12 years of age) an elevated production of estrogen occurs again, which leads to a maturation of the inner and outer gender attributes.
After puberty is past, around 250'000 germ cells pro ovary remain. With the onset of a regular cycle a nearly linear decline commences that with 40 years of age increases.
With the continuous decrease of the follicle cell count the production of estrogen is also reduced constantly. With roughly 50 years of age when follicles are no longer present, the estrogen production ceases and menopause ensues
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Commentary
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It is assumed the dictyotene stage of meiosis represents a special condition for oocytes that exhibits great stability with regard to outer physical and chemical influences. In contrast, the earlier stages, especially the pachytene, are more sensitive.
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