Endocrine-disrupting chemicals (EDCs) are synthetic or natural compounds that interfere with the endocrine system, inducing harmful effects on organisms depending on the dose and period of exposure. Numerous studies have identified concerning amounts of EDCs in environmental and human samples. The thyroid gland is essential for thyroid hormone production and controls several body functions. Several EDCs have been classified as thyroid disruptors, impairing thyroid hormone production, synthesis, metabolism, transport, and/or actions. Notably, thyroid disorders are the second most prevalent endocrine disease worldwide, with incidence increasing significantly in recent years. Some studies have correlated this rise in thyroid dysfunctions and cancers with increased exposure to EDCs. Although many EDCs are linked to thyroid dysfunction, this review focuses on the deleterious effects of plasticizers, organochlorine pesticides, and per- and poly-fluoroalkyl substances on thyroid function. These contaminants are commonly found in food, water, and everyday products. Although the impact of human exposure to these EDCs is controversial, numerous epidemiological, in vivo, and in vitro studies have indicated their harmful effects on thyroid function. Given the critical role of thyroid function and hormone production in growth, metabolism, and development, this review summarizes the consequences of exposure to thyroid disruptors for human health.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder in which the MECP2 (methyl CpG-binding protein 2) gene is mutated. Recent studies showed that RTT-derived neurons have many cellular deficits when compared to control, such as: less synapses, lower dendritic arborization and reduced spine density. Interestingly, treatment of RTT-derived neurons with Insulin-like Growth Factor 1 (IGF1) could rescue some of these cellular phenotypes. Given the critical role of IGF1 during neurodevelopment, the present study used human induced pluripotent stem cells (iPSCs) from RTT and control individuals to investigate the gene expression profile of IGF1 and IGF1R on different developmental stages of differentiation. We found that the thyroid hormone receptor (TRalpha 3) has a differential expression profile. Thyroid hormone is critical for normal brain development. Our results showed that there is a possible link between IGF1/IGF1R and the TRalpha 3 and that over expression of IGF1R in RTT cells may be the cause of neurites improvement in neural RTT-derived neurons.

Introduction: During the formation of neural circuits, the developing brain demonstrates extraordinary plasticity, heavily influenced by hormones. These chemical messengers interact with specific receptors to regulate vital physiological functions. The thyroid gland plays a pivotal role in maintaining hormonal balance and guiding brain development. However, emerging threats like endocrine-disrupting chemicals (EDCs) can interfere with this intricate system. EDCs are exogenous substances that can mimic, enhance, or block the actions of endogenous hormones, disrupting hormonal signaling in the brain at various developmental stages. Exposure can impair cognitive function and behavior due to disruptions in thyroid function. Studies indicate that mixtures of EDCs negatively impact brain development, leading to lower IQ and behavioral problems. Reducing EDC exposure through regulations and public awareness is crucial, and further research is needed to elucidate their mechanisms. Conclusions: Protecting vulnerable populations, such as pregnant women and children, is essential through prompt regulatory measures.

Environmental contamination from mixtures of chemical substances and materials resulting from anthropogenic activities has adverse effects on aquatic biota. Fipronil (FP) is an insecticide widely used in agriculture and public health and is frequently detected in environmental compartments. Microplastics (MPs) represent another class of contaminants that have raised concerns due to their ability to adsorb pollutants, potentially acting as a vector. This study evaluated the influence of polyethylene microplastics on the toxicity of FP in zebrafish (Danio rerio) embryos/larvae. Zebrafish embryos were exposed to aqueous suspension containing purified FP and the FP + MP mixtures for 120 h. Mortality, teratogenicity and cardiotoxicity were observed during the zebrafish development. Larvae were more sensitive to FP than the embryo. The presence of MPs reduced lethality; however, no significant changes were observed for sublethal endpoints. Our findings demonstrate the acute impact of FP on zebrafish embryos/larvae, demonstrating that MPs interfere with toxicity. Therefore, understanding the mechanisms of interaction between contaminants of different classes is essential for predicting the associated risks to biota.

Thyroid hormones (THs) are essential for brain development, and their dysregulation is associated with cognitive deficits and neurodevelopmental disorders. Down syndrome (DS), caused by trisomy 21, is frequently associated with thyroid dysfunction and impaired neurogenesis. Here, we investigated THs signaling dynamics during neural differentiation using human induced pluripotent stem cells (hiPSCs) derived from individuals with DS and controls. We analyzed the gene expression of key THs regulators—deiodinases, transporters, and receptors—and downstream target genes in hiPSCs, hiPSC-derived neural progenitor cells (NPCs), hiPSC-derived astrocytes, and hiPSC-derived neurons. DS-derived hiPSCs, hiPSC-derived NPCs, and hiPSC-derived neurons exhibited 2- to 7-fold increases in the gene expression of DIO2 and 3- to 8-fold reductions in DIO3, alongside 1- to 3-fold downregulation of THRA and THRB isoforms. hiPSC-derived astrocytes showed a 4-fold decrease in the gene expression of DIO2, a 4-fold increase in DIO3, upregulation of SLC16A10 (2-fold), and downregulation of SLC7A5 (0.5-fold) and THs receptors (0.5- to 12-fold). hiPSC-derived neurons exhibited marked downregulation of the gene expression of HOMER1 (0.5-fold), GRIN3A (14-fold), and GRIN3B (4-fold), accompanied by impaired spontaneous activity in multi-electrode array recordings. These findings reveal a robust, cell-type-specific imbalance between THs availability and signaling competence in DS hiPSC-derived neural cells, providing mechanistic insight into THs-related contributions to the function of DS hiPSC-derived neural cells and identifying potential therapeutic targets.