The toxic effects of polychlorinated biphenyl (Aroclor 1242) on Tm3 Leydig cells

Abstract

Polychlorinated biphenyls (PCBs) are ubiquitous and persistent environmental contaminants that disrupt endocrine function in biological systems, especially in the male reproductive system. Previous studies on the reproductive toxicity of PCBs have focused on the impairment of spermatogenesis, disruption of steroidogenesis, decreased sperm number, and infertility. Aroclor 1242 is a commercial mixture with an average of 42% chlorine by weight. The purpose of the present study was to elucidate the hazardous effects of Aroclor 1242 on Leydig cells through an evaluation of cell viability, lipid peroxidation, hydroxyl radicals, HO production, antioxidant enzymes, and steroidogenic enzymes. Leydig cells were exposed to Aroclor 1242 for 24 h under basal and luteinizing hormone-stimulated conditions at different concentrations (ranging from 10 M to 10 M). After incubation, Leydig cells were measured for cell viability, lipid peroxidation, reactive oxygen species (hydroxyl radical and HO), antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase), and steroidogenic enzymes (3β-hydroxysteroid dehydrogenase [HSD] and 17β-HSD). The results showed that cell viability was reduced only at Aroclor 1242 concentrations of 10 M and 10 M, whereas lipid peroxidation and reactive oxygen species increased relative to the concentration. Furthermore, antioxidant systems and steroidogenesis were interrupted to varying degrees, relative to the concentration. These findings suggest that exposure to Aroclor 1242 at high concentrations may result in detrimental effects to Leydig cell homeostasis. In addition, Aroclor 1242 may impair steroidogenesis, especially testosterone biosynthesis, by inhibiting two important steroidogenic enzymes.

Reproductive Function in a Population of Young Faroese Men with Elevated Exposure to Polychlorinated Biphenyls (PCBs) and Perfluorinated Alkylate Substances (PFAS)

“…Experimental in vivo studies have, however, shown that elevated exposure to PCBs disrupts and diminishes Leydig cell function in adult rats [ 44 , 45 , 46 ], and exposing lactating rats to Aroclor 1242, a PCB mixture of varying amounts of mono- through heptachlorinated homologs, caused significant adverse effects on Leydig cell function, reducing the capacity to produce T in response to LH stimulation in adult male offspring [ 47 ]. Another study of the toxic effects of Aroclor 1242 on Tm3 Leydig cells suggested that exposure to Aroclor 1242 at high concentrations may result in detrimental effects to Leydig cell homeostasis and impaired steroidogenesis, especially T biosynthesis, by inhibiting two important steroidogenic enzymes [ 48 ]. Further, PCBs are known to affect a variety of liver functions [ 49 , 50 ] and PCB-induced hepatic SHBG synthesis could therefore play a possible role contributing to the increased serum-SHBG concentrations observed.…”

Environmental contaminants and male infertility: Effects and mechanisms

“…A similar kind of effect on StAR and P450 ssc mRNA expression has been noted in guinea pigs treated with fluoride and aluminium (Dong et al, 2016). Mouse Leydig cells exposed to Aroclor 1,242, a commercial mixture of PCBs, resulted in reduced Leydig cell viability and impaired testosterone biosynthesis by inhibiting two steroidogenic enzymes (3β-hydroxysteroid dehydrogenase [HSD] and 17β-HSD) (Aydin & Erkan, 2017). In adult male rats, organochlorines, namely lindane and methoxychlor, have been reported to alter the testicular levels of StAR protein, androgen-binding .…”

“…Several animal studies have been conducted to examine the deleterious effects of various environmental toxicants on male fertility and decipher their possible mechanism(s) of action (Akarca-Dizakar et al, 2019;Albert, Nardelli, Lalancette, Hales, & Robaire, 2018;Aydin & Erkan, 2017;Campos et al, 2019;Kim, Cheon, Choi, & Lee, 2019;Kolatorova et al, 2018). The focus of this review is to shed light on the impact of environmental contaminants on male reproduction and the underlying mechanism of action based on the recent scientific data available.…”

“…Testosterone plays a vital role in the initiation and maintenance of spermatogenesis, differentiation of male genital organs and development of secondary sexual characteristics.Any factor that affects Leydig cell viability and/or interferes with testicular steroidogenesis can lead to the disruption of endocrine regulation of spermatogenesis and impairs fertility. Environmental contaminants are known to impair steroidogenesis by exerting an inhibitory effect on one or more steps in the steroidogenic pathways(Aydin & Erkan, 2017;Maske, Dighe, Mote, & Vanage, 2020;Singh & Singh, 2019) (Table 2).…”

Avaliações toxicológicas das alterações genotóxicas e epigenóticas induzidas por Aroclor 1254 em testí­culo, espermatozóides, fí­gado e rim de camundongos

“…Um dos principais mecanismos de ação dos PCBs é a indução de estresse oxidativo (ALY,H. A. et al, 2017;ALY, H. A.;ABDEL-NAIM, 2009;AYDIN; ERKAN, 2017).…”