**2. EDCs induce reproductive system toxicity: ultrastructural, cellular and molecular changes**

The male reproductive system is composed by two testes, a system of genital ducts, the accessory glands (seminal vesicles, prostate, Cowper and Littre glands) and the penis [15]. Testes, the male sexual glands, are ovoid organs localized outside the abdominal cavity within the scrotum. This localization maintains the temperature at 2–4°C lower than the body temperature, optimal for the testes function. Testes are surrounded by two different layers of protective tissue, the *tunica albuginea* and the *tunica vaginalis*. The testicular parenchyma is composed of one to three seminiferous tubules, the functional unit of the testis, and of interstitial tissue surrounding the tubules that contain the Leydig cells (LC), which are responsible for the production of T in the presence of luteinizing hormone (LH) (**Figure 1**) [16]. The seminiferous tubules are composed of male germ cells (spermatogonia, spermatocytes and spermatids) and Sertoli cells (SC). SC are involved in the mechanical support and nutrition of germ cells, regulation of male germ cell proliferation and differentiation, phagocytosis, steroid hormone synthesis and metabolism and maintenance of the integrity of seminiferous epithelium. The male reproductive system is responsible for the production of spermatozoa, for the synthesis and secretion of male sex hormones and for the delivery of male gametes into the female reproductive tract. The process of spermatogenesis is highly regulated by the hypothalamic-pituitary-gonadal (HPG) axis.

Evidences suggest that the normal morphology and function of the male reproductive system are affected by several factors including environmental pollutants (**Figure 1**) (e.g., EDCs). In addition to altered testicular morphology and dysfunction, exposure to EDCs also increased the incidence of testicular pathologies. For instance, exposure to phthalates was associated with the development of testicular cancer, cryptorchidism and hypospadias [17]. This section discusses the current knowledge on reproductive system EDC toxicity in humans and other animals.

**23**

**Figure 1.**

*The Role of Endocrine-Disrupting Chemicals in Male Fertility Decline*

**2.1 Changes in volume/weight of reproductive organs**

*Schematic representation of the effects of EDCs on HPG axis and testicular morphology.*

The volume/weight of the male reproductive organs is an important indicator of the integrity of this system. Several animal studies showed a significant decrease in the weight of the testes and sex accessory tissues in animals exposed to EDCs [4, 18–23]. For instance, male rats treated with 10 and 20 mg/(kg day) of TCS revealed a significant decrease in the weight of the testes, epididymis, ventral prostate, vas deferens and seminal vesicles [18]. However, an administration of 5 mg/(kg day) of TCS did not cause significant change in the testes and sex accessory tissues [18]. Recently, Lan et al. [4] showed that the absolute

*DOI: http://dx.doi.org/10.5772/intechopen.88330*

*The Role of Endocrine-Disrupting Chemicals in Male Fertility Decline DOI: http://dx.doi.org/10.5772/intechopen.88330*

*Male Reproductive Health*

male subfertility or infertility status.

**and molecular changes**

the hypothalamic-pituitary-gonadal (HPG) axis.

tive health.

effects on human health and are contributing to the trends in occurrence of male reproductive health problems and the decline in male fertility [3]. According to the literature, male reproductive decline may result from a combination of morphological, functional and molecular alterations in the reproductive organs, often due to exposure to EDCs. Most studies are focused either on the evaluation of basic seminal parameters or reproductive outcomes, but there are evidences that EDCs may impact at the level of the reproductive and endocrine systems. For example, there are evidences that TCS has a tendency to bioaccumulate in the epididymis [4]. Bisphenol A (BPA) has been reported to have both estrogenic and antiandrogenic effects [5–7]. It has been also negatively associated with sperm quality [8–10]. Toxicological studies showed that BPA caused adverse reproductive outcomes, namely, decreased epididymal weight, daily sperm production and testosterone (T) levels in rodents [11–13]. Recently, our group performed a systematic review regarding the effect of exposure to mercury (Hg) on human fertility [14]. Results revealed that higher levels of Hg in blood and hair were associated with

This chapter summarizes the effects of male exposure to EDCs on markers of male fertility. The agents discussed here, which include TCS, BPA, metals (such as cadmium (Cd) and Hg), polychlorinated biphenyls (PCBs) and others were chosen based on their human exposure prevalence and adverse effects on human reproduc-

**2. EDCs induce reproductive system toxicity: ultrastructural, cellular** 

The male reproductive system is composed by two testes, a system of genital ducts, the accessory glands (seminal vesicles, prostate, Cowper and Littre glands) and the penis [15]. Testes, the male sexual glands, are ovoid organs localized outside the abdominal cavity within the scrotum. This localization maintains the temperature at 2–4°C lower than the body temperature, optimal for the testes function. Testes are surrounded by two different layers of protective tissue, the *tunica albuginea* and the *tunica vaginalis*. The testicular parenchyma is composed of one to three seminiferous tubules, the functional unit of the testis, and of interstitial tissue surrounding the tubules that contain the Leydig cells (LC), which are responsible for the production of T in the presence of luteinizing hormone (LH) (**Figure 1**) [16]. The seminiferous tubules are composed of male germ cells (spermatogonia, spermatocytes and spermatids) and Sertoli cells (SC). SC are involved in the mechanical support and nutrition of germ cells, regulation of male germ cell proliferation and differentiation, phagocytosis, steroid hormone synthesis and metabolism and maintenance of the integrity of seminiferous epithelium. The male reproductive system is responsible for the production of spermatozoa, for the synthesis and secretion of male sex hormones and for the delivery of male gametes into the female reproductive tract. The process of spermatogenesis is highly regulated by

Evidences suggest that the normal morphology and function of the male reproductive system are affected by several factors including environmental pollutants (**Figure 1**) (e.g., EDCs). In addition to altered testicular morphology and dysfunction, exposure to EDCs also increased the incidence of testicular pathologies. For instance, exposure to phthalates was associated with the development of testicular cancer, cryptorchidism and hypospadias [17]. This section discusses the current knowledge on reproductive system EDC toxicity in

**22**

humans and other animals.

**Figure 1.** *Schematic representation of the effects of EDCs on HPG axis and testicular morphology.*
