Unhealthy levels of phthalates and bisphenol a in mexican pregnant women with gestational diabetes and its association to altered expression of miRNAs involved with metabolic disease
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Several studies indicate that bisphenol A (BPA) and phthalates may have a role in the development of metabolic diseases using different molecular pathways, including epigenetic regulatory mechanisms. However, it is unclear whether exposure to these chemicals modifies serum levels of miRNAs associated with gestational diabetes mellitus (GDM) risk. In the present study, we evaluated the serum levels of miRNAs associated with GDM (miR-9-5p, miR-16-5p, miR-29a-3p and miR-330-3p) and urinary levels of phthalate metabolites (mono-n-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono(2-ethyl hexyl) phthalate (MEHP)) and bisphenol A in GDM patients and women without GDM during the second trimester of gestation. We observed higher levels of miR-9-5p, miR-29a-3p and miR-330-3p in sera of patients with GDM compared to non-diabetic subjects. Phthalates were detected in 97–100%25 of urine samples, while BPA only in 40%25. Urinary MEHP and BPA concentrations were remarkably higher in both study groups compared to previously reported data. Unadjusted MEHP levels and adjusted BPA levels were higher in non-diabetics than in GDM patients (p = 0.03, p = 0.02). We found positive correlations between adjusted urinary MBzP levels and miR-16-5p expression levels (p < 0.05), adjusted MEHP concentrations and miR-29a-3p expression levels (p < 0.05). We also found negative correlations between unadjusted and adjusted MBP concentrations and miR-29a-3p expression levels (p < 0.0001, p < 0.05), unadjusted MiBP concentrations and miR-29a-3p expression levels (p < 0.01). Urinary MEHP levels reflect a striking exposure to di(2-ethylhexyl) phthalate (DEHP) in pregnant Mexican women. This study highlights the need for a regulatory strategy in the manufacture of several items containing endocrine disruptors in order to avoid involuntary ingestion of these compounds in the Mexican population. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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Bisphenol A; Circulating miRNAs; Endocrine disruptors; Gestational diabetes; Phthalates; Urinary metabolites 4,4' isopropylidenediphenol; biological marker; circulating microRNA; diisobutyl phthalate; microRNA; microRNA 16; microRNA 29a; microRNA 330; microRNA 9; mono (2 ethyl hexyl) phthalate; mono benzyl phthalate; mono isobutyl phthalate; mono n butyl phthalate; phthalic acid; phthalic acid benzyl butyl ester; phthalic acid dibutyl ester; unclassified drug; 4,4' isopropylidenediphenol; benzhydryl derivative; microRNA; phenol derivative; phthalic acid; phthalic acid derivative; adult; Article; body mass; clinical article; controlled study; epigenetics; female; gene expression; human; limit of detection; liquid chromatography-mass spectrometry; metabolic disorder; metabolite; Mexican; oral glucose tolerance test; pregnancy diabetes mellitus; pregnant woman; RNA extraction; second trimester pregnancy; ultra performance liquid chromatography; upregulation; blood; chemistry; gene expression regulation; genetics; metabolism; metabolome; Mexico; pregnancy; pregnancy diabetes mellitus; urine; Adult; Benzhydryl Compounds; Diabetes, Gestational; Female; Gene Expression Regulation; Humans; Metabolome; Mexico; MicroRNAs; Phenols; Phthalic Acids; Pregnancy; Pregnancy Trimester, Second; Up-Regulation
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