Perfluorooctanesulfonic acid (PFOS) disrupts cadherin-16 in the developing rat thyroid gland

Abstract

Perfluorooctanesulfonic acid (PFOS) can disrupt the thyroid hormone (TH) system in rodents, potentially affecting perinatal growth and neurodevelopment. Some studies also suggest that gestational exposure to PFOS can lead to lower TH levels throughout life, indicating that PFOS may compromise thyroid gland development. To address this question, we utilized a rat thyroid gland ex vivo culture system to study direct effects of PFOS on the developing thyroid. No significant changes to follicular structure or size were observed with 1 µM or 10 µM PFOS exposure. However, the transcription factor Foxe1, together with Tpo and Lrp2, were upregulated, whereas the key transcription factor Pax8 and its downstream target gene Cdh16 were significantly downregulated at the transcript level, observed with both RT-qPCR and RNAscope. Notably, Cdh16 expression was not uniformly downregulated across Cdh16-postive cells, but instead displayed a patchy expression pattern across the thyroid gland. This is a significant change in expression pattern compared to control thyroids where Cdh16 is expressed relatively uniformly. The disrupted expression pattern was also seen at the protein level. This suggests that PFOS exposure can impact follicular growth and structure. Compromised follicle integrity, if irreversible, could help explain reduced TH synthesis postnatally. This view is supported by observed changes to Tpo and Lrp2 expression, two factors that play a role in TH synthesis.

Keywords

• PFAS
• PFOS
• Thyroid
• Development
• Ex vivo
• Cadherin 16