PFOS-induced thyroid hormone system disrupted rats display organ-specific changes in their transcriptomes

Area of Science:

• Environmental Toxicology
• Endocrinology
• Molecular Biology

Background:

• Perfluorooctanesulfonic acid (PFOS) is a persistent environmental contaminant known to interfere with the thyroid hormone system.
• Thyroid hormones (THs) are regulated by the hypothalamic-pituitary-thyroid (HPT) axis, liver, and potentially gut microbiota.
• Xenobiotics like PFOS can disrupt TH homeostasis through various mechanisms and at multiple sites.

Purpose of the Study:

• To investigate the effects of PFOS exposure on the thyroid hormone system in adult male rats.
• To analyze transcriptomic changes in key organs (hypothalamus, pituitary, thyroid, liver) and assess the role of gut microbiota.

Main Methods:

• Adult male rats were exposed to PFOS (3 mg/kg/day for 7 days).
• Separate groups received vancomycin to modulate gut microbiota, with or without PFOS.
• Transcriptomic analysis (RNA sequencing) was performed on hypothalamus, pituitary, thyroid, and liver tissues.

Main Results:

• PFOS exposure led to decreased thyroxine (T4) and triiodothyronine (T3) levels, characteristic of hypothyroxinemia, without altering thyroid-stimulating hormone (TSH).
• Significant differentially expressed genes (DEGs) were identified in the hypothalamus (50), pituitary (68), thyroid (71), and liver (181).
• PFOS effects were not significantly altered by vancomycin-induced gut microbiota changes. DEGs in the hypothalamus and liver were linked to vesicle transport, neuronal signaling, and xenobiotic metabolism, not direct HPT axis gene regulation.

Conclusions:

• PFOS exposure disrupts thyroid hormone homeostasis, primarily by affecting TH metabolism and transport, as indicated by transcriptomic changes in the liver and hypothalamus.
• The pituitary and thyroid glands show minimal transcriptional response to PFOS, suggesting they are not primary sites of disruption.
• Gut microbiota modulation did not significantly alter the observed effects of PFOS on the thyroid hormone system in this study.