Perigestational exposure to low doses of PBDE-47 induces excessive ER stress, defective autophagy and the resultant apoptosis contributing to maternal thyroid toxicity

The Science of the Total Environment
Pei LiShun Zhang

Abstract

Brominated flame retardant 2,2',4,4'‑tetrabromodiphenyl ether (PBDE-47) is known to induce developmental neurotoxicity by disturbing thyroid hormones (THs). Evidence shows that maternal THs are crucial for brain development and growth of fetuses and infants. However, little is known about the effects of PBDE-47 on maternal thyroid status and its mode of action. Here, using female Sprague-Dawley rats orally exposed to low doses of PBDE-47 (0.1, 1.0, 10 mg/kg/day) from pre-pregnancy until weaning of offspring to mimic human exposure, we show that perigestational exposure to PBDE-47 elevated serum triiodothyronine and thyroxine levels in mother rats. This is accompanied by disrupted thyroid follicle structure including expanded follicles, hyperplastic epithelial cells and shed cell remnants filled in the exhausted follicular lumen. Mechanistically, PBDE-47 enhanced apoptosis in thyroid tissue, as demonstrated by Caspase-3 activation, PARP cleavage and DNA fragmentation. Further study identified that PBDE-47 upregulated the levels of GRP78, ATF4, active Caspase-12 and CHOP, suggesting endoplasmic reticulum (ER) stress and unfolded protein response activation. Moreover, PBDE-47 reduced the levels of LC3-II, an autophagy marker prote...Continue Reading

Citations

Jul 17, 2020·Journal of the Endocrine Society·Tomomi KurashigeYuji Nagayama
Jul 23, 2020·Environmental Pollution·Naga Raju MaddelaMallavarapu Megharaj
Nov 8, 2020·Molecular and Cellular Endocrinology·Jingwen ZhangXizeng Feng
Apr 28, 2020·Ecotoxicology and Environmental Safety·Ming-Hong SunShao-Chen Sun

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.