Effects of metal oxide inhalation on the transcription of some hormone receptors in the brain, examined in an in vivo mouse model

TL;DR

This study shows that inhaling metal oxide nanoparticles from welding fumes can disrupt hormone receptor activity in the mouse brain, especially in the hypothalamus and olfactory bulb.

Contribution

The study reveals region-specific and time-dependent changes in hormone receptor transcription in the brain after welding fume exposure.

Findings

The hypothalamus and olfactory bulb showed significant changes in estrogen, thyroid, and PPAR receptor expression after welding fume exposure.

ERβ, TRα, and PPARγ upregulation suggests a compensatory neuroprotective response to neuroinflammation.

Findings support the theory that metal oxides reach the CNS via the lungs-blood-BBB pathway, making certain brain regions more vulnerable.

Abstract

Respirable metal oxide nanoparticles in welding fumes pose significant health risks upon inhalation, potentially leading to neurodegenerative diseases. While the exact mechanisms remain unclear, it is evident that metal oxide nanoparticles can disrupt cellular functions, including metabolism and inflammatory responses after crossing the blood–brain barrier (BBB). Our study investigates the impact of manual metal arc welding fumes on hormone receptor transcription in an in vivo mouse model. After collecting samples from six different brain regions at 24 and 96 h upon exposure, we focused on expression levels of estrogen receptors (ERs), thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors (PPARs) due to their roles in modulating neuroprotective responses and neuroinflammatory processes. Analysis revealed differential susceptibility of brain regions to hormonal disruption induced by welding fumes, with the hypothalamus (HT) and olfactory bulb (OB) showing prominent changes in receptor expression. Considering ERs, 24 h sampling showed an elevation in OB, with later increases in both ERα and ERβ. HT showed significant ERβ change only by 96 h. TRs mirrored ER patterns, with notable changes in OB and less in HT. PPARγ followed TR trends, with early upregulation in HT and downregulation elsewhere. These findings suggest a compensatory response within the CNS aimed at mitigating neuroinflammatory effects, as evidenced by the upregulation of ERβ, TRα, and PPARγ. The coordinated increase in ERs, TRs, and PPARs in the hypothalamus and olfactory bulb also highlights their potential neuroprotective roles in response to welding fume exposure. Our results also support the theory of metal oxide penetration to the CNS via the lungs-blood-BBB pathway, making HT and OB more vulnerable to welding fume exposure.

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