Tribondeau A et al. (2024), Overlapping action of T3 and T4 during Xenopus ...

XB-ART-60640

Front Endocrinol (Lausanne) 2024 Jan 01;15:1360188. doi: 10.3389/fendo.2024.1360188.

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Overlapping action of T3 and T4 during Xenopus laevis development.

Tribondeau A , Du Pasquier D , Benchouaia M , Blugeon C , Buisine N , Sachs LM .

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Thyroid hormones are involved in many biological processes such as neurogenesis, metabolism, and development. However, compounds called endocrine disruptors can alter thyroid hormone signaling and induce unwanted effects on human and ecosystems health. Regulatory tests have been developed to detect these compounds but need to be significantly improved by proposing novel endpoints and key events. The Xenopus Eleutheroembryonic Thyroid Assay (XETA, OECD test guideline no. 248) is one such test. It is based on Xenopus laevis tadpoles, a particularly sensitive model system for studying the physiology and disruption of thyroid hormone signaling: amphibian metamorphosis is a spectacular (thus easy to monitor) life cycle transition governed by thyroid hormones. With a long-term objective of providing novel molecular markers under XETA settings, we propose first to describe the differential effects of thyroid hormones on gene expression, which, surprisingly, are not known. After thyroid hormones exposure (T3 or T4), whole tadpole RNAs were subjected to transcriptomic analysis. By using standard approaches coupled to system biology, we found similar effects of the two thyroid hormones. They impact the cell cycle and promote the expression of genes involves in cell proliferation. At the level of the whole tadpole, the immune system is also a prime target of thyroid hormone action.

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Species referenced: Xenopus laevis
Genes referenced: alb bcl6 casp3 ccna2 ccnb1 cdk1 cdk2 cdkn1a dio1 dio2 dio3 e2f1 fn1 itga3 itga5 klf9 lig1 mcm2 mcm4 mcm5 mcm6 mcm7 notch1 plk1 pola1 pold1 pole prkcd psme3 ptpn6 rpa2 rpa3 rxra rxrb rxrg sf3a1 skp2 slc16a10 slc16a2 slc5a5 slco1c1 snrpg thra thrb tpo traf3 trhr tshb ttr zbtb16
GO keywords: cell proliferation [+]

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	Figure 1 T3 and T4 treatment induce similar biological responses. (A) Differentially expressed (DE) genes up- and downregulated with T3 (red) and T4 (blue). (B) Type of regulation for each DE gene. (C) Rate of genes expression level between T3 and T4 condition. (D) Expression level of thyroid signaling related genes. “.L” and “.S”: genes located on long or short chromosome, respectively. DE genes with both T3 and T4. DE genes with T3. *DE genes with T4. pval ≤ 0.05. (E) Biological processes involved in T3 and T4 responses.
	Figure 2 T3 and T4 impact same pathways and most of DE hubs. (A) Network of gene (products) interactions. (B) The first 10 KEGG pathways containing most of DE genes in both conditions. (C) Expression level of DE hubs. “.L” and “.S”: genes located on long or short chromosome, respectively. (D) Biological processes impacted by DE hubs and deducted from a protein–protein interaction analysis.
	Figure 3 T3 and T4 responses concentrate in same subnetworks. (A) Subnetworks of gene (products) regulated by T3 and T4. (B) Principal biological processes impacted by the huge subnetwork and deducted from a protein–protein interaction analysis. (C) Principal biological processes impacted by small subnetworks and deducted from a protein–protein interaction analysis.