PFAS Compounds PFOA and Gen X are Teratogenic to Sea Urchin Embryos

Lion, A. T.; Bodine, S. M.; McCutcheon, K. R.; Ghogale, M.; Chandragiri, S.; Abayawardena, D.; Shrestha, B. D.; Descoteaux, A. E.; Alvarez, K.; Balkman, J. A.; Cocke, B.; Wikramanayake, A.; Schlezinger, J.; Wong, J. Y.; Prakash, V. N.; Bradham, C.

doi:10.1101/2024.11.21.624751

bioRxiv · 10.1101/2024.11.21.624751

PFAS Compounds PFOA and Gen X are Teratogenic to Sea Urchin Embryos

Lion, A. T.·Bodine, S. M.·McCutcheon, K. R.·Ghogale, M.·Chandragiri, S.·Abayawardena, D.·Shrestha, B. D.·Descoteaux, A. E.·Alvarez, K.·Balkman, J. A.·Cocke, B.·Wikramanayake, A.·Schlezinger, J.·Wong, J. Y.·Prakash, V. N.·Bradham, C.

View original source ↗Export metadata ↓

Abstract

Per-and polyfluorinated substances (PFAS) are synthetic chemicals that are used to make fluoropolymer coatings found in many products, such as non-stick pans, clothing, cosmetics, and food packaging. These highly persistent molecules are known as "forever chemicals" since they neither degrade environmentally nor break down enzymatically within biological systems. PFAS compounds readily contaminate water sources, and as a result, certain PFAS molecules have bioaccumulated in exposed species including humans. The purpose of this study was to define the effect of two PFAS molecules, the ostensibly more toxic perfluorooctanoic acid (PFOA) and the more recent, reportedly safer chemical hexafluoropropylene oxide dimer acid (Gen X), on the development of Lytechinus variegatus sea urchin embryos. We examined the effects of PFOA and Gen X on development and patterning using morphological analysis, immunostaining, HCR-FISH, and Particle Image Velocimetry (PIV). The results show that both PFAS compounds are teratogenic to sea urchin embryos. PFOA and Gen X each function at different intervals during development and provoke distinct phenotypic and gene expression outcomes. Despite beliefs that Gen X would be a safer alternative, our findings indicate that Gen X has earlier and more severe effects on endomesoderm and dorsal-ventral axis specification, neural development and function, and pattern formation compared to PFOA. These results illustrate the dangerous teratogenic potential of environmentally accumulating PFAS like Gen X, underscoring the negative ecological implications that accompany continuing commercial and industrial use of PFAS in the absence of remediation strategies. HIGHLIGHTSO_LIGen X is more teratogenic in sea urchins than PFOA C_LIO_LIGen X acts earlier than PFOA and perturbs axial and germ layer specification C_LIO_LIEach PFAS reduces neural numbers and perturbs ciliary behavior and swimming C_LI

Source connections

Published article ↗

Explore related subjects

developmental biology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Lion, A. T., Bodine, S. M., McCutcheon, K. R., Ghogale, M., Chandragiri, S., Abayawardena, D., Shrestha, B. D., Descoteaux, A. E., Alvarez, K., Balkman, J. A., Cocke, B., Wikramanayake, A., Schlezinger, J., Wong, J. Y., Prakash, V. N., Bradham, C.. 2024-11-21. PFAS Compounds PFOA and Gen X are Teratogenic to Sea Urchin Embryos. https://doi.org/10.1101/2024.11.21.624751

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Whole embryo barcoding reveals convergent origins of mesodermal cells during mammalian gastrulation

Classical fate-mapping and recent single-cell trajectory studies have suggested that mesoderm diversification during gastrulation proceeds through progressive fate bias and branching lineage segregation. Here, we combine inducible CRISPR-based lineage recording with single-cell RNA sequencing to reconstruct clonal relationships across mouse embryos barcoded at primitive streak onset and analyzed at early organogenesis. Mesodermal clones diverged after streak formation, but their developmental outputs remained extensively overlapping, revealing a clonal architecture that is not a simple branching lineage tree. Using sampling-aware statistical models, we quantify distinct clonal origins of paraxial mesoderm across the anterior-posterior axis, show that endothelial cells arise from multiple mesoderm origins but demonstrate transcriptional differences that correspond to anatomical position and clonal lineage, and identify clonal sharing between extra-embryonic mesoderm and embryonic derivatives, including cardiac lineages and a shared hindlimb-allantois progenitor. In the heart, progenitors corresponding to classical heart fields remain multipotent, contributing both myocardial and non-myocardial cell types. Together, our findings support a model in which mesodermal diversity is assembled through spatially distinct, fate-biased progenitor pools whose descendants converge on shared cell states. Our findings challenge simple branching models of mesoderm diversification and provide a clonal framework for understanding how tissue diversity emerges in the embryo.

developmental biology↗

bioRxiv2026

Transcription factor handover reshapes hub dynamics to coordinate temporal progression of Notch response

To decipher information in space and time, cells require mechanisms to sustain gene expression programmes once an initial signal decays. Localised condensation of transcription complexes into hubs is emerging as a key step in gene regulation and, by combining live imaging of transcription and of transcription complexes at target loci, we have investigated how these evolve to enable a prolonged transcription outcome in response to Notch signalling. Measuring the dynamics of hindsight (hnt) transcription reveals two phases. The first, a probabilistic response similar to E(spl)-C genes, is directly controlled by Notch and the second, a sustained response, is indirectly controlled through the BTB transcription factor Broad. The two phases correlate with a transition in transcription factor enrichment at hnt: complexes of Notch coactivator Mastermind and of Broad are successively enriched. Notably, the lifetime of the hubs formed by each are distinct and correlate with the change in transcription profiles. These reflect the binding dynamics of each complex, with Broad having significantly more stable association with chromatin, forming longer lasting hubs and yielding sustained transcription. Furthermore at intermediate stages we detect hubs containing both Broad and Mam implying an evolution in hub composition. Together our data support that the dynamic properties of transcription hubs are crucial for the probability and dynamics of transcription and point towards a ''hub handover'' in enabling temporal progression in gene expression responses.

developmental biology↗

bioRxiv2026

An interplay of multilayered regulatory mechanisms underlies the RNA solubility phase transition during vertebrate oocyte-to-embryo transition

Dynamic RNA-protein interactions influence RNA transport, storage, stability, and activity and are fundamental to a broad range of biological processes. During the oocyte-to-embryo transition (OET), fully differentiated gametes fuse and regain totipotency. Throughout the OET, the transcription remains silent. Spatiotemporal regulation of gene expression relies on the dynamic interactions between maternal transcripts and various protein complexes. Despite its fundamental importance, RNA-protein interaction dynamics at the global level during the OET remain poorly understood. Here, we leverage fractionation RNA-seq to profile RNA insolubility, a proxy for the interaction between RNAs and protein complexes, during zebrafish OET. We identify transcripts that transition between the soluble (relatively protein-free) and insoluble (heavily protein-associated) states and demonstrate that these phase transitions are driven by ribosome-dependent and ribosome-independent mechanisms. We demonstrate that the capacity of maternal RNAs to engage with protein complexes changes dynamically during the OET through remodeling of cis-regulatory features. We developed a machine-learning framework and uncovered multiple cis- and trans-regulatory features that may contribute to RNA insolubility. To validate these predictions, we examined poly(A) tail length and m6A dynamics. We found that poly(A) tail length is associated with both ribosome-dependent and ribosome-independent RNA phase transitions. In parallel, fractionation m6A-pulldown RNA-seq revealed highly dynamic changes in the m6A landscape during the OET. A correlation between m6A modifications and RNA insolubility is gradually established during the OET. Together, our findings uncover a multilayered regulatory mechanism governing RNA phase transitions during the OET, providing fundamental insights into post-transcriptional regulation of gene expression during development.

developmental biology↗