spermatogenesis is under analysis. Oct4, a nuclear transcription factor, also appears to be critical for the origin of PGCs since it is expressed in cell lineages that give rise to PGCs as well as in PGCs and oocytes but not in sperm once they are in the testes.
Figure 2.4. Genes and other factors involved in PGC migration and differentiation.
Clearly, we could spend many chapters on this topic for there is much more to be known about molecular determinants and their functions in germ plasm formation and gametogenesis. The point to be made here is that current molecular methods, coupled with traditional approaches are beginning to shed light on a problem that is fundamental to life and that has concerned scientists for over 100 years.
Our understanding of human development has come from the extensive knowledge gained from pure research on lower animals. Such past and present research continues to guide ongoing research in human embryology and development. Early during development, the fate of the primordial germ cells is determined by endogenous factors (determinants) in lower animals. As expected, the determinants have been found to be genetically controlled. Specific mRNAs appear to be the cytoplasmic determinants that underlie the formation of germ cells. Some likely candidates have been identified and soon the whole molecular and cellular story of germ cell determination will be revealed. Humans share similarities in some of the genes that control germ cell formation. After the PGCs have migrated into the genital ridges, external factors (including hormones) will now influence their further development. Cells that get lost, don't get influenced by a normal set of factors and, as a result, in some instances can form cancerous teratomas. In the female, the number of germ cells increases by mitosis which then stops so that only a limited number of eggs are possible. In fact, as we will see in the next chapter, millions of potential eggs will die. In the male, mitosis and meiosis continue throughout life so a continual supply of sperm is available. The stage is now set for the formation of eggs and sperm. The next chapter examines oogenesis.
Chapter 3
Life and Death in the Ovary
The female produces eggs from primordial germ cells that have entered her genital ridges during embryonic development. The process of egg formation thus begins in the embryo and continues into the adult. In this chapter, we will first examine the structure of the female anatomy finally focusing in upon the ovaries where oogenesis (egg formation) occurs. We will examine the development of the egg follicle and the layers of cells and extracellular material that surrounds the egg prior to ovulation. We'll then quickly remind you about the important role of hormones in the reproductive cycle of females, a topic that is covered in detail in physiology books. The role of hormones in sexual maturation and reproduction is not covered in detail in this book.
Development of the External Genitalia
While most students understand the fundamentals of human anatomy, not everyone does. For this reason and because it is important to put every process and event into perspective, it is important for us to know the reproductive anatomy of the female if we are to first appreciate where and how eggs are formed and later released prior to fertilization. Before we look at the mature female anatomy, let's take a quick look at the development of the external genitalia as shown in Figure 3.1. Later, when we examine the early development of the male genitalia we'll become aware of some very basic similarities between the two events.
Figure 3.1. The development of the external female genitalia.
Female Genital Tract
The graphic below shows the internal female genital tract (Figure 3.2). On the left the various structures are named and these names will be used in future chapters. On the left the route the sperm and eggs will take within the female genital tract is shown by colored arrows. Follow the pathway for sperm entry into the genital tract (green arrows) and that of the egg after release from the ovary (gold arrows) and its movement into and down the fallopian tube. Fertilization, as will be discussed in Chapter 6, occurs in the upper region of the fallopian tubes approximately where the green and gold arrows meet.
Figure 3.2. The female genital tract.
The female genital tract is specifically designed to:
•Produce ova
•Accept sperm
•Control the process of fertilization
•Provide a site for implantation of the egg
•Provide an environment and the essentials for fetal development
Each of these points will be discussed in more detail as we move through this and future chapters.
The Ovary and Follicle Development
The ovary doesn't appear to be a very organized structure. Each stage of oogenesis and follicle maturation is haphazardly strewn throughout both the left and right ovaries. However, since it is not the goal here to be reproductive anatomists, we will use a typical textbook example of the ovary which organizes components for us (Figure 3.3).
Figure 3.3. The structure of the ovary and development of ovarian follicles.
The above figure emphasizes the sequential events in follicle development. During embryogenesis the first follicles that form are called primordial follicles: the granulosa is one cell layer thick and the oocyte is arrested (has stopped developing) at prophase I of meiosis. Over time there is an increase in the number of granulosa cells as they become stratified and become referred to as the theca. As well, the fluid filled cavity or antrum around the oocyte continues to fill with follicular fluid. In keeping with these changes, the follicles are progressively named primary, secondary and tertiary (or mature) follicles. In the figure, the follicle cells (green), follicular fluid (cyan) and developing oocyte (magenta) have been colored to clearly demonstrate the changes in the follicle as the egg matures and is finally ovulated. Subsequently, the follicle undergoes changes as it becomes a hormone producing corpus luteum (gold, dark green).
The ovaries also play a role in regulating the status of the uterus. Estrogen, released from the maturing follicles, causes the uterine epithelial lining to proliferate in preparation for the arrival of a fertilized egg. Progesterone released from the corpus luteum will further mature the uterine lining causing it to enter the secretory phase which will be able to interact with the blastocyst should fertilization occur and embryonic development begin. These hormonal changes plus many others controlled by the pituitary lead to the monthly menstrual cycle of females, a topic covered in detail in physiology books.
Sequence of Events in Oogenesis
After migrating into the gonadal ridge (female genital ridge) the primordial germ cells become oogonia (sing. oogonium) (Figure 3.4). Oogonia are the primary source of future eggs but they only undergo mitosis in the embryo producing about seven million potential eggs. In females, germ cells (oogonia) typically undergo a total of ~24 cell divisions.
