Polychlorinated biphenyls (PCBs), chlorinated pesticides, and mercury are global environmental contaminants that can disrupt the endocrine system in animals and humans. However, there is little evidence that they can interfere with endocrine status in pregnant women and neonates at low levels of exposure. The aim of this study was to examine thyroid hormone levels during pregnancy and in cord blood in relation to blood concentrations of organochlorine compounds (OCs) and Hg in healthy women recruited during pregnancy. We found a significant negative correlation between maternal total triiodothyronine levels and three non-coplanar congeners (PCB-138, PCB-153, and PCB-180), three pesticides (p,p´-DDE, cis-nanochlor, and hexachlorobenzene), and inorganic Hg independently, without any other changes in thyroid status. No significant relationships were observed between OCs and cord serum thyroid hormones. Cord serum free thyroxin was negatively correlated with inorganic Hg. These results suggest that at even low levels of exposure, persistent environmental contaminants can interfere with thyroid status during pregnancy.
Context
Underlying mechanisms leading to gestational diabetes mellitus (GDM) are still under investigation, and it is unclear whether the placenta plays a role in triggering glucose intolerance or if its functions are modified in response to the hyperglycemia. Circulating miRNAs are involved in placental development and function and are encapsulated in extracellular vesicles (EVs).
Objective
To compare differential expression of miRNAs in circulating EVs in pregnancies complicated by GDM vs controls.
Methods
This was a case-control study nested in a prospective pregnancy cohort including 23 women with GDM and 46 matched controls. The presence of serum EVs in early pregnancy was validated by transmission electron microscopy. Placental dimensions were assessed at 11 to 13 weeks of gestation. Differential expression of 17 miRNAs encapsulated in EVs (miR‒122-5p, miR‒132-3p, miR-1323, miR‒182-3p, miR‒210-3p, miR‒29a-3p, miR‒29b-3p, miR‒342-3p, miR‒517-5p, miR‒517a-3p, miR‒518b, miR-520h, miR‒525-5p, miR‒136-5p, miR‒342-3p, miR‒376c-5p, and miR‒494-3p) was assessed using quantitative reverse transcription PCR.
Results
EVs were present in the early phase of placentation (6 to 15 weeks of gestation) in both cases and controls. No differences were observed for placental dimensions and estimated placental volume between GDM and control groups. Ten miRNAs (miR‒122-5p; miR‒132-3p; miR‒1323; miR‒136-5p; miR‒182-3p; miR‒210-3p; miR‒29a-3p; miR‒29b-3p; miR‒342-3p, and miR-520h) showed significantly higher levels in GDM cases than in controls (P ≤ 0.05). Bioinformatics analysis showed that these miRNAs are involved in trophoblast proliferation/differentiation as well as in insulin secretion/regulation and glucose transport in pregnant women.
Conclusion
The miRNA content of blood EVs may be a promising avenue for studying the early effect of impaired glucose metabolism on placental development.
Thyroid hormones play a critical role in the growth of many organs, especially the brain. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) interact with the thyroid pathway and may disturb neurodevelopment. This prospective study was designed to examine associations between maternal blood PBDEs and PCBs in early pregnancy and levels of thyroid hormones in maternal and umbilical-cord blood. Levels of low-brominated PBDEs, 3 PCB congeners, total and free thyroid hormones (triiodothyronine (T3) and thyroxine (T4)), thyroid-stimulating hormone, thyroid peroxidase antibodies, iodine, selenium, and mercury were measured in 380 pregnant women in the first trimester who were recruited at the University Hospital Center of Sherbrooke (Quebec, Canada) between September 2007 and December 2008. Thyroid hormone levels were also assessed at delivery and in cord blood (n = 260). Data were analyzed on both a volume basis and a lipid basis. At less than 20 weeks of pregnancy, no relationship was statistically significant in volume-based analysis. In lipid-based models, an inverse association between maternal PBDEs and total T3 and total T4 and a direct association with free T3 and free T4 were observed. At delivery, in both analyses, we observed negative associations between maternal total T4, free T3, cord-blood free T4, and PBDEs and between maternal free T3 and PCBs. Our results suggest that exposure to PBDEs and PCBs in pregnancy may interfere with thyroid hormone levels.
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