The female and male reproductive systems develop selectively as a result of specific hormonal signals (sex-determining region on the Y chromosome, anti-Mullerian hormone, testosterone/5α-dihydrotestosterone, and estrogens) that lead to further development or regression of embryological structures. Additional hormones (gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone, progesterone, and human chorionic gonadotropin) influence further development and subsequent adult functions, including the menstrual cycle, fertilization and pregnancy, lactation, and oogenesis/spermatogenesis. These hormones work via signaling proteins, including several variations of G proteins, to selectively activate or inhibit these developmental and functional events.
BASIC ANATOMY AND DEVELOPMENT
The reproductive system is derived from the intermediate mesoderm and includes the reproductive organs of both males and females derived from the Wolffian ducts (male), Mullerian ducts (female), and the gonads (male and female), including the testes and ovaries. The influence of hormones and biochemical signals in the formation and activity of the reproductive system is vastly important and, when these signals go awry, disease ensues.
During the initial stages of gestation, all humans begin with both Wolffian and Mullerian ducts and the development of male and female embryos is indistinguishable. At about gestational day 56, further growth and development into male or female sexual organs is dependent on the effects of the sex-determining region of the Y chromosome (sry). In the genetic male, the sry product binds to deoxyribonucleic acid (DNA) and distorts it dramatically out of shape. This alters the properties of the DNA and likely alters the expression of a number of genes. One of these genes produces anti-Mullerian hormone (AMH), a dimeric, glycoprotein hormone also known as Mullerian inhibiting factor (MIF). AMH is produced by Sertoli cells in the testes and signals, via its receptor, a member of the transforming growth factor (TGF)-β I and II receptor family. Binding of AMH to TGF-β type II receptor allows it to bind to the type I receptor. The type I receptor is then able to phosphorylate serine and/or threonine amino acids to activate transcription factors in the nucleus, which regulate gene expression. The presence of AMH leads to full development of the Wolffian ducts and male structures; only a few remnants of the Mullerian ducts survive in males.
In males, the Leydig cells also appear and testosterone synthesis begins, leading to male sexual characteristics, including testis formation. Testosterone’s effect on the seminiferous tubules (see below) is also critical for modulating signaling and gene expression and, therefore, male development (Figure 20-1). In the absence of sry, embryos spontaneously develop into phenotypic females. With no sry product, AMH and testosterone are not produced and the Wolffian ducts regress with only a few remnants remaining. The mechanism of AMH suppression of Mullerian duct formation is unknown. Further development of the Mullerian ducts creates the female sexual organs and structures. In both sexes, the Wolffian duct is responsible for development of the bladder trigone.