Impact of Endocrine Disruptors on the Genitourinary Tract

Abstract

Over the last decades, the human species has seen an increase in the incidence of pathologies linked to the genitourinary tract. Observations in animals have allowed us to link these increases, at least in part, to changes in the environment and, in particular, to an increasing presence of endocrine disruptors. These can be physical agents, such as light or heat; natural products, such as phytoestrogens; or chemicals produced by humans. Endocrine disruptors may interfere with the signaling pathways mediated by the endocrine system, particularly those linked to sex hormones. These factors and their general effects are presented before focusing on the male and female genitourinary tracts by describing their anatomy, development, and pathologies, including bladder and prostate cancer.

Keywords: bladder; cervix; endocrine disruptor; genitourinary tract; hormone; ovary; prostate; testicles; urethra; uterus.

Figure 1

Sources of EDC contamination. EDCs from various origins, such as industrial chemicals, can directly contaminate soil and water by spilling or as rain carries the contaminants in the fumes. Heavy metals are also present in many industrial processes. Plastics and inks used for receipts can also contaminate food or the environment when they become garbage. Pesticides are widely used in agriculture and can contaminate soil, water sources, and produce. Natural EDCs, such as phytoestrogens, can also be present in certain products like soya. Finally, pharmaceutical and cosmetic/personal care industries use many EDCs in various production processes. All these contaminants can negatively affect the health of humans and animals, especially those in direct contact with polluted water, like fish and amphibians.

Figure 2

Mechanisms of action of EDCs. EDCs can interact through various mechanisms, such as hormonal receptors. These interactions can lead to dysregulated hormonal levels, availabilities, and distribution, ultimately impairing the actions of endogenous hormones in their target tissues. Furthermore, some EDCs possess off-target effects and may interact directly with cells and the genome. The ten different mechanisms of action are detailed in Section 2.2. This figure was inspired by the review from La Merrill et al. [59].

Figure 3

Multisystem effects of EDCs on human health. Various EDCs, such as bisphenols, phthalates, pesticides, dioxin, and phytoestrogens, can impact human biological systems, including endocrine, nervous, immune, pulmonary-cardiovascular, and reproductive systems. These effects vary widely and have significant implications for overall human health.

Figure 4

Schema of the female reproductive system. The female reproductive system is composed of the ovaries, which produce the oocytes, and the fallopian tubes, which allow the transport of these cells to the uterus, where fecundation takes place. The uterus comprises several structures, including the endometrium and myometrium, to host the embryo and nourish its development. The vagina is the muscular canal that serves during intercourse and delivers the baby during childbirth.

Figure 5

Development of the genital organs in utero. Hormones tightly regulate the differentiation of genitalia in men and women. These organs are highly responsive to hormonal signaling from the beginning of their development and throughout adulthood to perform their functions. Female genital organs are represented in pink, whereas male genital organs are depicted in blue. AMH: anti-Mullerian hormone; AR: androgen receptor.

Figure 6

Schemas of the male reproductive system. The male reproductive system is depicted in the left panel. More detailed prostate and testis structures are presented in the right panels.

Figure 7

Sera level of sex hormones during lifetime. Sera level of sex hormones throughout lifetime is reported in males (upper panel) and females (lower panel). For clarity, the x–axis (age) is shared by both panels and was truncated for adulthood before menopause. The level of hormone in the sera is represented as a relative value.