Correlation of Endocrine Disrupting Chemicals Serum Levels and White Blood Cells Gene Expression of Nuclear Receptors in a Population of Infertile Women

Abstract

Significant evidence supports that many endocrine disrupting chemicals could affect female reproductive health. Aim of this study was to compare the internal exposure to bisphenol A (BPA), perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), monoethylhexyl phthalate (MEHP), and di(2-ethylhexyl) phthalate (DEHP) in serum samples of 111 infertile women and 44 fertile women. Levels of gene expression of nuclear receptors (ERα, ERβ, AR, AhR, PXR, and PPARγ) were also analyzed as biomarkers of effective dose. The percentage of women with BPA concentrations above the limit of detection was significantly higher in infertile women than in controls. No statistically significant difference was found with regard to PFOS, PFOA, MEHP and DEHP. Infertile patients showed gene expression levels of ERα, ERβ, AR, and PXR significantly higher than controls. In infertile women, a positive association was found between BPA and MEHP levels and ERα, ERβ, AR, AhR, and PXR expression. PFOS concentration positively correlated with AR and PXR expression. PFOA levels negatively correlated with AhR expression. No correlation was found between DEHP levels and all evaluated nuclear receptors. This study underlines the need to provide special attention to substances that are still widely present in the environment and to integrate exposure measurements with relevant indicators of biological effects.

Bisphenol a and the female reproductive tract: an overview of recent laboratory evidence and epidemiological studies

“…In particular , increased BPA levels are correlated with a decrease in peak estradiol levels and decreased oocyte retrieval number [10,44]. A similar mechanism of action may underlie the association between female infertility and higher BPA levels that has been consistently reported in the results of the Italian biomonitoring study PREVIENI [11,45]. Interestingly, in this study, the higher serum BPA levels in infertile women were also correlated with upregulation of some nuclear receptors (ERα, ERβ, Androgen receptor, and Pregnane-X receptor) in the serum mononuclear cells [11,45].…”

Phthalates and perfluorinated alkylated substances in Atlantic bluefin tuna (Thunnus thynnus) specimens from Mediterranean Sea (Sardinia, Italy): Levels and risks for human consumption

“…[40,41] Since both phthalates and PFASs show toxicity and prolonged exposure can affect endocrine function and cause neurodevelopmental disorders and infertility we have calculated the estimated daily ingestion of the contaminants of interest through tuna consumption. [42][43][44][45][46][47][48][49] The tolerable daily intake (TDI) established for DEHP is 0.05 mg/kg, a value that was used in this work as a basis of comparison for the intake of DEHP itself and for the total amount of DEHP and MEHP, being the latter a direct metabolite of DEHP. [12] We calculated the EDI for the general Italian population and for those who claimed to be fish consumers, assuming that their daily fish intake consisted solely of Atlantic bluefin tuna fillets (Table 3).…”

Egr1 is rapidly and transiently induced by estrogen and bisphenol A via activation of nuclear estrogen receptor-dependent ERK1/2 pathway in the uterus

“…It suggests that BPA is able to disturb uterine environments with respect to aberrant expression of genes important for embryo implantation. In fact, a recent study showed that infertile women tend to have significantly detectable serum BPA compared to women with proven fertility [34]. Interestingly, the women with the relatively higher levels of BPA in their urine had possibility to have twice the chance of implantation failure [13].…”