Xenobiotics reproductive toxicity

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... 

Any xenobiotic associated with adverse effects on development of male or female reproductive function can be classified as a reproductive toxicant (Evans, 2007 Rogers and Kavlock, 2008). Even chemicals adversely affecting animal well-being have a potential negative impact on development and reproductive function. This chapter will attempt to focus on toxicants which are available for or could arise from military and terrorist activities and specific mechanisms of actions which have a direct effect upon the male and/or female reproductive tract or which target normal embryonic and/or fetal growth and maturation (Evans, 2007). 

Tissues used in toxicogenomics studies Most toxicogenomics studies to date have involved hepatotoxicants [23,36, 38-44,47,49,50,52-55,57,59,60,204], as the liver is the primary source of xenobiotic metabolism and detoxification and because liver injury is the principal reason for withdrawal of new drugs from the market [205]. Toxicogenomics studies have also addressed nephrotoxicity [44,45,51], neurotoxicity [206,207], reproductive toxicity [48], as well as lung toxicity [39,56], skin toxicity [208], and cardiotoxicity [209]. 

Any reproductive toxicant capable of endocrine disruption can also be considered an endocrine-disrupting chemical (EDC) or an endocrine disrupter. Another term frequently used with respect to endocrine disruption, especially regarding xenobiotics that interact with endogenous hormone receptors, is hormonally active agent (HAA). In most instances, "EDC," "endocrine disrupter," or "HAA" can be used interchangeably to discuss the actions of a given xenobiotic (Evans, 2007). 

In real life , humans and animals can be exposed to some toxicants both pre- and postnatally. Many organic xenobiotics have the potential to bioaccumulate within exposed individuals, possibly affecting future generations by way of genetic and epigenetic effects. However, reproductive endpoints, such as conception rates and sperm counts, are relatively insensitive, and subtle, toxicant-induced changes in reproductive efficiency can be overlooked or missed (Evans, 2007). 

Receptor-xenobiotic interactions have been associated with immune, central nervous (CNS), endocrine, cardiovascular (CVS), developmental, and reproductive system effects as well as with carcinogenesis. A sampling of toxic chemicals that bind with receptors and their effects is listed in Table 4.3. 

Toxic infertility as used here refers to adverse effects on the reproductive systems of human males and females that result from exposure to xenobiotic single chemicals and chemical mixtures. This infertility may be because of direct toxic effects on the male or female reproductive organs and endocrine systems, or on the developing fetus such that the fetus cannot be either conceived or carried to term after conception. Developmental toxicity, the onset of adverse effects on the developing fetus or child after birth are discussed in Chapter 24. 

Human infertility can result from the action of xenobiotic chemicals on the female reproductive system, the male reproductive system, attack on the fetus, and the induction of effects in utero that are manifest during adulthood, giving rise to a programmed infertility. Spontaneous abortion can ensue when pregnant women are exposed to toxic chemicals such as those in disinfection byproducts produced by the chlorination of drinking water. 

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