Lecture given at OMR&RCA Biennial Conference
1-3 May 2009
The life of a new organism of the human species starts at the moment of fertilization. This is when the sperm and oocyte plasma membranes fuse. The ovarian continuum begins at fertilization, when the zygote starts its development.
Until now, a biological dogma has been that all sex differences in the brain arise from differences in the gonadal secretions. It has recently been demonstrated that the whole genome of males and females seems to be different; not only are the sexual chromosomes different, but also autosomes have a major role in sexual differentiation. For our purposes this will be very important to keep in mind, because during this
lecture I would like to invite you to look at ourselves the way we were created. I would also like to invite you to look at the many instances by which this creation can be distorted.
Approximately 2 months after fertilization occurs, the future oogonia, called primordial germ cells at this time, leave the embryo and migrate to the vitelline sac in order to escape the process of cell differentiation. Some four weeks later these cells migrate to the region of the future ovary, the gonadal crest, and start their process of differentiation, forming millions of primordial follicles. At this time some 7 million primordial follicles are formed, most of which will undergo atresia. When the girl is born, 1 to 2 million follicles containing the oocytes remain. Of these, about 475 will complete folliculogenesis during ovulation.
Figure 1. Human Embryo at three weeks.
The brain of the embryo is also developing. During pre natal and early neonatal development, there is a sensitive period for hormone dependent sexual differentiation.
There are also other periods of big hormonal changes during a woman’s lifetime. One of these periods is puberty. Pubertal maturation of the hypothalamic–pituitary–gonadal (HPG) axis begins with activation of neurons that secrete gonadotrophin releasing hormone (GnRH).
GnRH is produced by thousands of neurons located in the hypothalamus and secreted in a pulsating fashion, by the so called GnRH pulse generator. The permissive signals that allow the initiation of puberty vary with sex. Girls have their pubertal development one year earlier than boys.
Puberty, viewed from the perspective of reproduction, could be considered as the process by which hormonal changes take place in order to permit the expulsion from the ovary of mature oocytes, thus allowing fertilization to take place. Follicular development, which lasts 85 days, has two phases: a gonadotrophin (GnRH) independent phase lasting 71 days and a gonadotrophin dependent phase that lasts 14 days. The menstrual cycle represents the gonadotrophin dependent phase of follicular development.
GnRh pulses produce the Follicle Stimulating Hormone (FSH) that stimulates follicles with an antral cavity.
Figure 2. Main follicular development phases.
During the first 2 years after menarche, occasional anovulatory cycles may occur. These cycles may be longer or shorter; however, subsequently a healthy girl will exhibit regular monthly ovulations, characterized by a 25 to 36 day cycle. The data in Figure 3 shows that cycles get within this length after one or two years post menarche.
Figure 3. Variability of cycle length by age.
Sometimes it is believed that it is normal to be irregular during teenage years. This is not a normal condition, but of course we all know it happens. Table 4 shows the classification of menstrual cycles.
Table 4. What is normal?
|Classification||Number of days|
|Short Cycle||< 24|
|Normal||24≤ Cycle ≤ 36|
|Long Cycle||> 36|
|Ovulatory||9 ≤ Luteal phase ≤ 16|
|Anovulatory||Luteal phase < 9|