Abstract
The female and male reproductive tracts originate from the same embryonic/fetal tissue. The gonads and internal and external genitalia begin as bipotential tissues. The indifferent gonad consists of a medulla and cortex. Human female and male embryos develop in the same way for the first 6 weeks, regardless of genetic sex (46,XX or 46,XY karyotype) (Figure 1.1). The one way to tell the difference between 46,XX and 46,XY embryos during this time period is by looking for a Barr body (“inactive” one X chromosome) or a Y chromosome. The medulla of the XY embryo will develop into the testes and the cortex will regress. In the XX embryo, the ovary will originate from the cortex and the medulla will decline. A complete 46,XX chromosomal complement is necessary for normal ovarian development. The second X chromosome contains elements essential for ovarian development.
The Fetal Gonads
The female and male reproductive tracts originate from the same embryonic/fetal tissue. The gonads and internal and external genitalia begin as bipotential tissues. The indifferent gonad consists of a medulla and cortex. Human female and male embryos develop in the same way for the first 6 weeks, regardless of genetic sex (46,XX or 46,XY karyotype) (Figure 1.1). The one way to tell the difference between 46,XX and 46,XY embryos during this time period is by looking for a Barr body (“inactive” one X chromosome) or a Y chromosome. The medulla of the XY embryo will develop into the testes and the cortex will regress. In the XX embryo, the ovary will originate from the cortex and the medulla will decline. A complete 46,XX chromosomal complement is necessary for normal ovarian development. The second X chromosome contains elements essential for ovarian development.
Figure 1.1 Human male and female embryos develop similarly for the first 6 weeks, regardless of genetic sex. MIS, Müllerian-inhibiting substance.
The Fetal Ovary
The development of the human ovary during fetal life can be divided into five stages:
1. Indifferent gonad stage
2. Stage of differentiation
3. Period of oogonia formation (mitosis and migration)
4. Period of oocyte formation (meiosis and differentiation)
5. Stage of follicle formation (follicle assembly)
The gonads begin with development from the mesothelial layer of the peritoneum. The ovary differentiates into a central part – the medulla, which is covered by a surface layer, called the germinal epithelium. At approximately 4–5 weeks of gestation, the paired gonads structurally form the gonadal ridges [1]. The immature ova originate from 50 to 80 germ cells of the dorsal endoderm of the yolk sac (Figure 1.2). These progenital or primordial germ cells (PGCs) multiply by mitosis, to yield approximately 30 000 at migration. By the time they reach the gonadal ridge (between 5 and 6 weeks of gestation), they are called oogonia (diploid stem cells of the ovary with underdeveloped endoplasmic reticulum and differentiated nucleus) [2–3]. The factors that initiate and direct the migration of the germ cells are not known. Migrating PGCs still express core pluripotency genes such as SOX2, OCT4, and NANOG that are characteristic for early embryonic stem cells [4]. After migration, PGCs begin to express Mvh [5], which marks the end of their migration and the beginning of sexual dimorphic development in the undifferentiated gonadal ridge and thus their development into primary oogonia. DAX1 is a gene typically expressed in both testicular and ovarian tissues (a short arm of the X chromosome). DAX1 downregulates the effectiveness of the male sex reversal Y gene (SRY) or its downstream elements, resulting in an ovary.
Figure 1.2 Human embryonic primordial germ cell (PGC) migration.
At approximately week 6–7 of development, in the absence of anti-Müllerian hormone (AMH) (from Sertoli cells), the Müllerian ducts develop into the female internal genitalia. The development of female internal and external structures is gonad independent.
The source of the gonadal somatic cells is still uncertain. Besides germ cells, the earliest recognizable gonad contains somatic cells derived from at least three different tissues: coelomic epithelium, mesenchyme, and mesonephric tissue. Ultrastructural studies have even suggested that both the coelomic epithelial and underlying mesonephric cells offer the somatic cells that are intended to become follicular cells. The germ cells are first identifiable at the end of the third week after fertilization and can be found in the primitive endoderm at the caudal end in the dorsal wall of the adjacent yolk sac. At 6–8 weeks, the first signs of ovarian differentiation are reflected by the rapid mitotic multiplication of germ cells, reaching 6–7 million oogonia by weeks 16–20 (Figure 1.3). Oogonia go into prophase of the first meiotic division and form clusters (oogonia surrounded by a single layer of flattened follicular cells) called primordial follicles.
