The Thyroid’s Plastic Predicament: From Blood-Barrier Breach to Transcriptional Dysregulation

Background: Microplastics (MPs, 1–5 mm) and nano plastics (NPs, <1 μm) are prevalent environmental contaminants with emerging evidence of endocrine disruption, particularly targeting the thyroid gland a master regulator of metabolism, development and homeostasis. Objective: This review synthesizes 2023–2026 evidence on MNPs thyroid toxicity, elucidating mechanisms from blood-thyroid barrier (BTB) penetration to transcriptional dysregulation, mammalian outcomes, associated chemical synergies, knowledge gaps and human health implications. Methods: Comprehensive analysis of peer-reviewed studies (n=45+) using PubMed/PMC/Scopus, focusing on in vivo/in vitro mammalian models, human biomonitoring and regulatory frameworks. Results: NPs breach fenestrated BTB capillaries via endocytosis, inducing ROS/NF-κB-mediated inflammation, TPO/NIS/Tg suppression, TBG/TTR displacement by additives (BPA/BPS/BPF, phthalates, PBDEs), THR antagonism and PAX8/CREB dysregulation. Rodent models show dose-dependent T3/T4 ↓ (40–60%), TSH ↑, follicular hypertrophy/fibrosis. Human data link placental MPs to neonatal T4 ↓ and occupational exposure to subclinical hypothyroidism. NPs exhibit 4–10× higher potency than MPs due to bioavailability/surface area. Conclusions: MNPs pose possible thyroid risk via multiple mechanisms justified by toxicokinetic, Pyrolysis GC-MS harmonization, longitudinal cohorts and precautionary policies. Pregnant women and children represent vulnerable populations.