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

Abstract

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% of urine samples, while BPA only in 40%. 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.

Phthalate Exposure and Long-Term Epigenomic Consequences: A Review

“…Several circulating miRNAs are dysregulated in patients diagnosed with gestational diabetes mellitus (GDM) during pregnancy (Zhao et al, 2011;Zhu et al, 2015). A study sought to identify the association of BPA and phthalate exposure measured in serum with the expression of circulating miRNAs related to GDM (miR-9-5p, miR-16-5p, miR-29a-3p, and miR-330-3p) revealed higher levels of miR-9-5p, miR-29a-3p, and miR-330-3p of patients with GDM compared to non-diabetic subjects (Martinez-Ibarra et al, 2019). Phthalate metabolites like MBP, mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), and MEHP were detected in 97-100% of urine samples and Bisphenol-A (BPA) in only 40% of samples (Martinez-Ibarra et al, 2019).…”

“…A study sought to identify the association of BPA and phthalate exposure measured in serum with the expression of circulating miRNAs related to GDM (miR-9-5p, miR-16-5p, miR-29a-3p, and miR-330-3p) revealed higher levels of miR-9-5p, miR-29a-3p, and miR-330-3p of patients with GDM compared to non-diabetic subjects (Martinez-Ibarra et al, 2019). Phthalate metabolites like MBP, mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), and MEHP were detected in 97-100% of urine samples and Bisphenol-A (BPA) in only 40% of samples (Martinez-Ibarra et al, 2019). Thus, phthalates and BPA may play a role in the development of metabolic diseases like GDM via epigenetic regulatory mechanism such as miRNA regulation.…”

Endocrine Disruptors in Food: Impact on Gut Microbiota and Metabolic Diseases

“…Phthalates have been considered obesogens, therefore contributing to overweightness and obesity. It has been shown that exposure to phthalates alters glucose and lipid metabolism, which increases the risk of developing insulin resistance [150,151].…”

Challenges to regulate products containing bisphenol A: Implications for policy

“…22 A more recent study noted that the exposure levels among Mexican pregnant women were 30 times higher than those reported in previous studies. 23 These studies are limited in sample size and target only pregnant women, which highlights the need for information about BPA levels in other Mexican population groups. In addition, in products commonly found in Mexican supermarkets, it has been shown that BPA migrated from the epoxy resin lining tuna and jalapeño cans into the enclosed food; 24 and that BPA is present in baby bottles and microwaveable plastic containers.…”