Abstract

Phthalates are substances used as plasticizing agents and solvents that can increase the risk of infertility and that appear to induce oxidative stress. The aim of the study was to show the possible relationship between urinary concentrations of phthalates metabolites, namely MEP, MBzP, MnBP, MEHP, MEHHP, and MnOP and biomarkers of nucleic acids oxidation, methylation, or protein nitroxidation. The oxidative stress biomarkers measured in human urine were 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, 8-oxo-7,8-dihydro-2′-deoxyguanosine, 3-nitrotyrosine, and 5-methylcytidine. Two hundred and seventy-four couples were enrolled, undergoing an assisted reproduction technology (ART) treatment, urine samples were analyzed in HPLC/MS-MS, and then two sub-groups with urinary concentration > 90th or <10th percentile were identified, reducing the sample size to 112 subjects. The levels of oxidative stress biomarkers were measured in both groups, reduced to 52 men and 60 women. A statistically significantly difference for 8-oxoGuo and 3-NO2Tyr between men and women, with higher levels in men, was found. The levels of oxidative stress biomarkers were directly correlated with some phthalate concentrations in both sexes.

Highlights

  • Exposure to phthalate seems to increase oxidative stress levels, which is recognized to contribute to male and female infertility

  • The phthalates with lower molecular weight are highly soluble in water (i.e., diethyl phthalate (DEP) and di-n-butyl phthalate (DnBP)) and they are inserted in production cycle of cosmetics, pharmaceuticals, and insecticides

  • The results showed higher levels of oxidative stress biomarkers for higher concentration of phthalate metabolites, confirmed in both groups

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Summary

Introduction

Exposure to phthalate seems to increase oxidative stress levels, which is recognized to contribute to male and female infertility. Phthalates are substances that exhibit endocrine disrupting properties and can induce problems related to infertility, disorders of the metabolic, immune, and thyroid systems [1]. They are a family of esters of phthalic acid, widely used in industry as plasticizing agents, added to improve the flexibility and moldability of plastics and widely used in children’s toys, medical devices, cosmetics, hygiene products, clothing such as footwear and raincoats, food packaging, and construction material [2]. DEHP, due to its toxicity for reproduction, has recently been replaced with di-isononyl phthalate (DiNP), in the production of PVC [3]. Phthalates, at high concentration, have toxic effects on the liver and kidneys, and cause malformations and fetal death

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