**2.2 Pyrethroids**

The most widely used group among pesticides is the group of synthetic pyrethroids. General population exposure to pyrethroids can occur primarily through dietary residues and inhalation or ingestion of contaminated house dust after indoor application. Because of high performance and low toxicity of pyrethroids, these chemicals are widely used both in agriculture and at home as a substitute for organochlorine insecticides [44, 45]. In recent years, hormone disruptors such as pyrethroids have been discussed with studies showing the male infertility relationship [28, 29]. It is suggested that pyrethroids can cross the blood testicular barrier, reach the nucleus of spermatogenetic cells, and affect sperm function, due to their hydrophobic and small molecular structure. Although associations between occupational exposure to pyrethroids and altered semen quality are generally reported, there are limited epidemiological data on the potential effects of non-occupational exposure to pyrethroids on male reproductive function [44]. In recent years, studies have reported that pyrethroid pesticides can reduce sperm count and motility, change sperm morphology, increase abnormal sperm count, cause sperm DNA damage, and also affect sex hormone levels [46–49]. It is emphasized that these findings may be of particular concern for male infertility due to increased use of pyrethroids and widespread human exposure. As a result, it is reported that these substances play an important role in reproductive toxicity [45].

The number of environmental pollutants such as pyrethroids determined to have anti-androgenic effects is increasing day by day. However, recently the relationship between androgenic/antiandrogenic effects of these substances and male infertility has been discussed [28, 29, 50, 51]. Androgens, like testosterone, are steroid hormones essential for normal male reproductive development and function and play a very important role in spermatogenesis, in adulthood [52]. Androgenes belong to the steroid superfamily and are mainly involved in gonadal development. Androgens are present in different levels in both men and women [27]. The differentiation of the male reproductive system depends on fetal testicular androgen production. In addition, disruption estrogen exposure in the fetal period may cause reproductive abnormalities by disrupting the sensitive androgen-estrogen balance [7, 27]. Antiandrogenic pyrethroids interfere with the androgen receptor signaling pathway by interacting with androgen receptors [51]. In recent years, cypermethrin, deltamethrin, fenvalarate, bifenthrin, permethrin, lambda cyholothrin, cyfluthrin are the most used pyrethroids in many countries, and the anti-androgenic effect of these substances has been reported [53–59]. Therefore, the identification of these chemicals is very important in many fields, including food production, reproductive toxicology, and risk assessment [57]. Although it has been suggested that some pyrethroids act as androgen receptor antagonists, more studies are needed to determine the mechanisms underlying the antagonism [50].

As a result of exposure to pyrethroids in different ways, it has been shown that these substances are rapidly metabolized in human by hydrolytic cleavage of the ester bond followed by oxidation [60]. Because of the rapid metabolism of pyrethroids, determination of their urinary metabolities is preferred for the estimation of pyrethroid exposures. 3-phenoxybenzoic acid (3-PBA) is a general metabolite of many pyrehroids (cypermethrin deltamethrin, permethrin, and others) and is a metabolite with the highest rate in non-occupational exposure. Therefore, determination of this metabolite in urine may indicate environmental exposure to different pyrethroids [44, 60]. In the literature, there are not many studies on the infertility relationship of anti-androgenic pyrethroids/metabolites [28, 29, 44, 46, 61]. In infertility studies, exposure to non-persistent pyrethroid metabolities has been associated with changes in reproductive hormones in men [62], as well as decreased semen quality and increased sperm DNA damage due to urinary metabolities of pyrethroid

#### *Endocrine Disruptors and Infertility DOI: http://dx.doi.org/10.5772/intechopen.104403*

insecticides [29, 44, 63]. Han et al. [60] found an association between serum hormone levels and urinary 3PBA levels (between 3-BPA and LH and E2 hormones), in infertile men, as result of their investigation. The detrimental effect of pesticides such as pyrethroids on sperm concentration, motility, and morphology may result from impaired spermatogenesis due to various hormonal changes [64]. The information provided by examining sperm morphology in a complete semen analysis is becoming increasingly important clinically for infertility and fertility [65]. Abnormal sperm morphology due to secretory dysfunction of Leydig and Sertoli cells impairs sperm fertilization capacity. Sperm parameters such as sperm concentration, sperm motility, and sperm morphology are related to each other. The factors that cause deterioration in any of these parameters generally affect the others. It is reported that the best indicator of infertility is sperm concentration after sperm motility [64, 66]. More studies are needed to better elucidate the effects of exposure to potential endocrine-disrupting pyrethroid pesticides on semen parameters.
