Abstract
To characterize polychlorinated biphenyls (PCBs) action on Leydig cells, PCBs congeners, low-chlorinated (delor 103; d103) and high-chlorinated ones (delor 106; d106) were selected. The cells were treated according to PCBs dose (d103 or d106 0.2 ng/ml in low doses:, or 2 ng/ml in high doses) and type (d103 + d106 in low doses or 103 + 106 in high doses). After 24 h treatment with PCBs, a distinct increase in estrogen-related receptors (ERRs type α, β and γ) expression was revealed. However, the dose- and type-dependent PCBs effect was mostly exerted on ERRα expression. A similar increase in ERRs expression was demonstrated by estradiol but not testosterone, which was without an effect on ERRs. PCBs caused no decrease in the membrane potential status of Leydig cells (either in dose or type schedule) but had severe effects on the mitochondria number and structure. Moreover, PCBs markedly increased calcium (Ca2+) concentration and sex steroid secretion (both androgens and estrogens were elevated). These findings suggest a similar estrogenic action of PCBs congeners (d103 and d106) on Leydig cell function. We report dose- and type-specific effects of PCBs only on Leydig cell ERRs expression. Both delors showed common effects on the mitochondria ultrastructural and functional status. Based on our results, ERRα seems to be the most sensitive to hormonal modulation. The increases in Ca2+ and sex steroid secretion may be due to the activation of ERRs by PCBs binding and/or direct effect of PCBs on ERRs mRNA/protein expression. Nevertheless, to confirm the existence of possible relationships between ERRs signaling (including PCBs as ligands) and mitochondria function in Leydig cells, further intensive studies are needed.
Highlights
Polychlorinated biphenyls (PCBs) were first manufactured commercially in the late 1920s
To determine whether PCBs alter the expression of ERRα, ERRβ and ERRγ at the mRNA level, MA-10 Leydig cells (Fig. 1a) were treated with low (0.2 ng/ml) and high (2 ng/ml) doses of delor 103 (d103l and d103h, respectively) and delor 106 (d106l and d106h, respectively) alone or in combinations (d103l + d106l and d106h + d106h, respectively) and were analyzed by reverse transcriptase (RT)-PCR (Fig. 1b–d, b’–d’)
Real-time RT-PCR analysis was applied to quantitatively evaluate estrogen-related receptors (ERRs) mRNA expression in Leydig cells that was normalized to GAPDH expression (Fig. 1b–d)
Summary
Polychlorinated biphenyls (PCBs) were first manufactured commercially in the late 1920s. In the late 1970s, evidence of their toxicity led to the institution of bans in many countries and to their inclusion on the list of compounds in the Stockholm Convention on Persistent Organic Pollutants of 2001 (UNEP 2001). These chemicals have been used in many different products, including electrical equipment, surface coatings, inks, adhesives, flame-retardants and paints. PCBs are regularly detected in human breast milk, serum and tissues. These compounds are able to pass through the human placenta (Koppe et al 1992). Other studies on rats have shown activation of microsomal enzymes of liver by PCBs (especially delor 106) indicating active mechanisms of PCBs metabolism in tissues (Butschak et al 1978)
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