Xenobiotics endocrine disruption

Sperm counts in men have declined by abont 50% during the time period 1940-1990, from an average of 113 million per mL of semen in 1940 to an average of 66 million in 1990. During the same time frame there has been a decrease in seminal volume from 3.40 to 2.75mL [55]. The reasons for the observed decline in semen quality are exposures to pesticide mixtures [56] and other xenobiotic endocrine disrupters [57], maternal consnmption of beef containing anabolic steroids [58], and other xenobiotics and tobacco smoking [59]. 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

Measurement of contaminants in fish has concentrated on muscle tissue since the aim has generally been to protect the health of the consumer rather than that of the fish. Endocrine tissue such as the gonads has been much more rarely examined, while data for adrenal, thyroid and pituitary levels are virtually non-existent. More data are available for the liver, as a lipid rich tissue and the major site of xenobiotic catabolism, but the concentrations have rarely been related to its capacity to produce vitellogenin or metabolise endogenous hormones. Tissue concentrations of a wide range of chemicals, are at a level which suggests that, either alone or in combination, they will cause significant endocrine disruption in fish in many polluted habitats. 

Xenobiotic induced disruption of female fertility follows essentially the same pattern as that of the male and can be caused by changes in pituitary-hypothalamic function, primary disruption of ovarian structure or hormone secretion, or changes in the rate of hormone deactivation. In addition, there may be changes in the synthesis of estrogen induced production of the yolk protein by the liver (vitellogenesis), which in turn can lead to failure to lay down sufficient yolk in the developing oocytes. Vitellogenesis provides a valuable biomarker for endocrine dysfunction in both sexes,but is more properly considered as part of the liver function. 

The liver plays an important role in the endocrine system. The concentrations of hormones in plasma, and the activity of the glands which secrete them, are determined by the rate at which they are deactivated by the liver. The liver also has a major function in female reproduction since it is the target tissue of ovarian estrogen, to which it responds by producing the yolk protein vitellogenin. " Xenobiotics that affect either of these functions can therefore be considered to be potential endocrine disrupters. 

Danzo BJ (1997) Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins. Environ Health Perspect 105 294-301... 

Modeling the endocrine disruption profile of xenobiotics. Recent Progr. Computat. Sci. Eng., 7A-, 1347-1351. 

Estevez-Alberola, M.C. and M.P. Marco. 2004. Immunochemical determination of xenobiotics with endocrine disrupting effects. Anal. Bioanal. Chem. 378 563-575. 

From these inventories and data, it is clear that society is facing an enormous problem of contamination. Many of the polluting compounds that are continuously dispersed are products of industrial activities such as phenols and halogenated phenols, polycyclic aromatic hydrocarbons (PAH s), endocrine disruptive chemicals (EDC), pesticides, dioxins, polychlorinated biphenyls (PCB s), industrial dyes, and other xenobiotics. In this chapter, we critically review the literature information on the enzymatic transformation of these polluting xenobiotics. This work is focused on peroxidases as enzymes able to transform a variety of pollutant compounds with the aim to reduce their toxicity and their environmental impact. 

Given this dependence on steroid hormones, endocrine-disrupting xenobiotics that affect the synthesis or actions of estradiol or progesterone are likely to disrupt embryo implantation or pregnancy. Indeed, the abortifacient action of the morning... 

Before we discuss endocrine-disrupting xenobiotics, it is important to understand both the functions of endogenous estrogens (female hormones) and androgens (male hormones) and how these hormones exert their actions. Estrogens and androgens perform numerous functions, many of which are similar in all classes of vertebrates. The major functions of these hormones are related to sex determination, sexual differentiation, and sexual development. 

For the purposes of this chapter, the term reproduction will be used primarily in reference to vertebrate species of animals (especially mammals) and will be inclusive of development (Figure 36.1), which is sometimes treated as a separate topic in toxicology texts. This particular chapter emphasizes what is currently known about the adverse effects of known chemical warfare agents and selected environmental contaminants on male and female reproductive function, as well as xenobiotic-induced effects on the growth, maturation, and sexual differentiation of the embryo and fetus. Endocrine disruption is an extremely common mechanism of action for xenobiotics associated with impaired reproductive function and will be discussed along... 

For the purposes of this chapter, reproductive toxicity will refer to any manifestations of xenobiotic exposure, including endocrine disruption (see discussion below), reflecting adverse effects on any of the physiological processes and associated behaviors and/or anatomical structures involved in animal reproduction or development (Figure 36.1). This is a fairly broad definition which encompasses developmental toxicity, as well as any toxic... 

Endocrine disruption which is independent of interactions between xenobiotics and endogenous hormone receptors can occur in a variety of different ways, including alterations in the number of hormone receptor sites (up- or down-regulation) or direct or indirect hormone modifications which alter hormonal function (Evans, 2007 Keith, 1997). Xenobiotics can change the rate of synthesis or destruction of endogenous hormones and can alter how hormones are stored, how they are released into and/or transported within the circulation, or even how they are eventually cleared from the body (Capen, 2008 Evans, 2007 Keith, 1997 Sikka et al, 2005). Any xenobiotic toxic to hormone-producing organs or tissues (e.g. testis and ovary) also has the potential to decrease hormone synthesis and thereby indirectly cause endocrine disruption (Devine and Hoyer, 2005 Evans, 2007). 

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