**Abstract**

Infertility is a multifactorial disease caused by both genetic and environmental factors. It is observed in 10–15% of couples, among which male infertility contributes for half the cases. Thus, identifying underlying causes of male infertility and for proper methods for treating and/or preventing sperm damage is of paramount importance. It is found that one of the factors that has been recently implicated in male infertility is oxidative stress, mediated by reactive oxygen species (ROS) that are produced during the metabolic process, as well as during the exposure to environmental chemical agents and their interaction with tissue-specific enzymes. Several studies have identified genetic variations at different loci, connected with male infertility, that may shed light on some idiopathic cases of seminal fluid abnormalities. In this chapter, we make an effort to decipher the contribution of polymorphisms in xenobiotic detoxification genes in the male infertility development.

**Keywords:** male infertility, xenobiotics, arylamine N-acetyltransferase 2, GSTM1, GSTT1, GSTP1, cytochrome P4501A1, genetic polymorphism, oxidative stress, DNA fragmentation, detoxification

### **1. Introduction**

Deterioration of male reproductive health has become a serious problem in most countries [1]. Contributing factors for male infertility comprise genital infections, ejaculatory duct obstruction (EDO), hypogonadism, varicoceles, or exposure to environmental factors (e.g., xenobiotics, ionizing radiation), lifestyle factors (e.g., alcohol, smoking and obesity), genetic causes, systemic diseases, and abnormal ejaculation [2]. However, in approximately 30–45% of male infertility cases, the etiology remains undetermined and is called the idiopathic infertility [3]. Genetic factors make a significant contribution to the development of idiopathic male infertility. For example, oligozoospermia and azoospermia have been recently determined to be tied with such genetic deviations as translocations, microdeletions and mutations [4] in genes that play a role in testicular development, gametogenesis and metabolism of xenobiotics associated with reproductive system disorders. Xenobiotic metabolism causes the main damage to the organism by creating covalent bounds with cellular macromolecules (DNA or protein). This indicates that the expression regulation and activity of xenobiotic-metabolizing enzymes may play the crucial role in determination of male reproductive system

susceptibility to chemically induced damages. Thus, xenobiotic-mediated adverse effects of male reproductive system are associated with the polymorphisms in xenobiotic detoxification genes. Different variants of one gene are categorized as polymorphism if their frequency in the population exceeds 1% [5]. In contrast to mutations, polymorphisms have indirect connections with particular seminal fluid abnormalities but may be indispensable during the investigation of multifactorial diseases. Polymorphic variants may change the expression or function of encoded protein, leading to its conformational changes that would result in different pharmacokinetics, chemical reaction capacities and efficiency of the xenobioticdetoxifying enzymes. In this chapter, we discuss polymorphisms in the main enzymes capable of maintaining the oxidants/antioxidants balance in reproductive tissues, focusing mainly on phase I cytochrome P4501A1 (CYP1A1) and phase II (GSTM1, GSTT1, GSTP1 and arylamine N-acetyltransferase 2 (NAT2)) detoxifying enzymes.
