Chapter 20

• The gonads possess a dual function: an endocrine function involving the secretion of sex hormones and a nonendocrine function relating to the production of germ cells (gametogenesis).
• Gametogenic and secretory functions of either the ovary or testes are dependent on the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary.
• The blood–testis barrier between the lumen of an interstitial capillary and the lumen of a seminiferous tubule impedes or prevents the free exchange of chemicals/drugs between the blood and the fluid inside the seminiferous tubules.
• Xenobiotics can act directly on the hypothalamus and the adenohypophysis, leading to alterations in the secretion of hypothalamic-releasing hormones and/or gonadotropins.
• Steroid hormone biosynthesis can occur in several endocrine organs including the adrenal cortex, ovary, and the testes.
• Female reproductive processes of oogenesis, ovulation, the development of sexual receptivity, coitus, gamete and zygote transport, fertilization, and implantation of the conceptus may be sites of xenobiotic interference.
• Xenobiotics may influence male reproductive organ structure, spermatogenesis, androgen hormone secretion, and accessory organ function.

Chemicals can adversely affect reproduction in males and females. Recent trends in human fertility point to the potential for declines in normal human reproduction and suggest that exposure to environmental chemicals and drugs may contribute to these declines. The reproductive cycle is outlined in Figure 20–1.

###### Figure 20–1

The reproductive cycle.

Numerous complex processes are orchestrated in a precise and sequential order for optimal performance at different stages of the life cycle of animals and humans. Following fertilization of an egg by a sperm, the resulting zygote must be transported along the oviduct while maturing into an early embryo. This embryo must then implant in the uterus successfully, differentiate, produce a placenta, and undergo normal embryogenesis and fetal development.

Acquisition of sexual maturity involves the generation of gametes by the gonads. For parental animals, once their reproductive life span has finished, the process of reproductive senescence then occurs. These processes all involve complex interplay between tissues and cells, under hormonal control that provides the critical signals and precise timing of these events. All these processes can be targets for the action of specific agents that can disturb events leading to adverse effects on reproduction, such that the normal production of viable offspring cannot occur.

During the seventh week of human gestation, the male and female morphological characteristics begin to develop. Gonadal differentiation depends on signals from the Y chromosome, which contains the genes necessary to induce testicular morphogenesis. One of these signals is the SRYgene, which is the sex-determining region on the short arm of the Y chromosome and acts as a “switch” to initiate transcription of other genes that contribute to testicular organogenesis. In the absence of the SRY protein, the gonad remains indifferent for a short period of time before differentiating into an ovary.

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