Three Structurally Different Polychlorinated Biphenyl Congeners (Pcb 118, 153, and 126) Affect Hormone Production and Gene Expression in the Human H295R In Vitro Model

Abstract

Polychlorinated biphenyls (PCB) are ubiquitous environmental pollutants that have been linked to adverse health effects including endocrine disruption. This study compared the mono-ortho-substituted PCB 118 and di-ortho-substituted PCB 153 with the non-ortho-substituted PCB 126, for possible effects on steroid hormone production and on the expression of 10 genes encoding proteins involved in steroidogenesis. The H295R human adenocarcinoma cell line was used as an in vitro model. Cells were exposed for 48 h to solvent control (dimethyl sulfoxide, DMSO) or 6 different concentrations ranging from 40 pM to 4 muM of one of the three test compounds. All three congeners significantly increased the production of estradiol-17beta. PCB 118 produced a rise in progesterone and cortisol in a concentration-dependent manner, similar to PCB 126. Testosterone was significantly reduced in response to PCB 153 but not PCB 118 or PCB 126. All three congeners elevated aldosterone at the highest concentration tested. A significant increase was observed in CYP11B2 mRNA levels in cells exposed to the three congeners. In addition, PCB 126 upregulated CYP19, 3beta-HSD2, StAR, and HMGR mRNA levels at the highest concentration tested, and downregulated CYP21 at 40 nM. In conclusion, all three PCB congeners are capable of modulating steroidogenesis in H295R in a concentration-dependent manner, whereby the hormone profile following PCB 118 exposure resembles that of PCB 126. Where changes in gene expression profile are concerned, exposure to PCB 126 showed the greatest effects.

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

“…The induction of CYP19 gene expression may be a possible mechanism for the increase in E2 and the decrease in T production. There were some cases in which the results of hormone production and CYP19 gene expression were consistent with each other [29]. Kraugerud et al found that PFOS caused a numerically higher level of E2 followed by a concentration-response relationship, and E2 was significantly elevated at 600 mM PFOS [30].…”

Role of Environmental Factors and Gonadotoxin Exposure in Unexplained Female Infertility

“…Earlier studies demonstrated disruption of estrus and menstrual cycles in rats and primates [112][113][114][115], and the negative effects of several PCB mixtures on the fertilizability of murine oocytes [116][117][118]. More recently, altered synthesis of estradiol, testosterone, and progesterone by human cell cultures was reported following treatment with individual PCB congeners [119]. The "dioxin-like" PCB congener #77 was also found to decrease fertilization potential in murine oocytes when female mice were fed a contaminated diet [120].…”

In vitro bioassays for the study of endocrine-disrupting food additives and contaminants

“…In addition, the H295R model was used to evaluate modulation of steroidogenic hormone production by single polychlorinated biphenyl (PCB) congeners [23], emerging pollutants (e.g., perfluorinated compounds) [24], and pharmaceuticals [19,71]. It was also deployed to look at effects of estrogenic mycotoxin, zearalenone, and the metabolites, a-and b-zearalenol.…”

“…Recent advances in cell biology and biotechnology have allowed development of a new generation of bioassays focused on hormonal nuclear receptor signaling [14][15][16][17][18] and steroidogenesis pathways [11,[19][20][21][22][23][24][25]. Some of these new bioassays are based on the ability to introduce specific properties and reporter genes into stable cellular systems.…”

“…Given the wide scope of potential working mechanisms and sites of action of EDCs, the review focuses on those bioassays measuring interference of EDCs with nuclear receptor signaling (see sub-section 2.1) or Has been applied to known food contaminants, either as single compound [20,23,24], or as mixtures [11,25] The hormone production (see sub-section 2.2), These mechanisms are very complementary and the bioassays and their use very well documented. We give attention to assays validated or being validated by control organizations.…”