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The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
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Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
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Environmental PFOA Exposure Alters Early Developmental Programming during the Maternal-Zygotic Transition.

Zainab Afzal1, Vandana Veershetty1, Evan Pittman1,2

  • 1The Julius L. Chambers Biomedical and Biotechnology Research Institute, North Carolina Central University, Durham, NC.

Biorxiv : the Preprint Server for Biology
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Summary

Per- and polyfluoroalkyl substances (PFAS) disrupt early zebrafish development during the maternal-to-zygotic transition (MZT). This critical window of embryonic gene regulation is highly susceptible to environmental contaminants, impacting developmental outcomes.

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Area of Science:

  • Developmental Biology
  • Environmental Toxicology
  • Genomics

Background:

  • Early embryogenesis relies on precise gene regulatory programs.
  • The maternal-to-zygotic transition (MZT) is a critical shift in developmental control.
  • Per- and polyfluoroalkyl substances (PFAS) are linked to developmental abnormalities, but their impact on MZT is unclear.

Purpose of the Study:

  • To investigate how PFAS exposure during MZT affects early embryonic gene regulation in zebrafish.
  • To identify the timing of MZT vulnerability to PFAS exposure.

Main Methods:

  • Zebrafish embryos were exposed to PFAS at different time points within the MZT window.
  • Transcriptomic analysis (qRT-PCR and RNA-seq) was performed at 24 hours post-fertilization.
  • Behavioral assays were conducted at 5 days post-fertilization.

Main Results:

  • PFAS exposure dysregulated genes involved in transcriptional activation, lineage specification, proliferation, and differentiation.
  • Widespread gene network perturbations were observed in transcriptional regulation, cell signaling, and morphogenesis.
  • Exposure during early MZT (3.5 hpf and 8 hpf) caused the most significant gene expression changes.
  • Early PFAS exposure led to altered larval behavior.

Conclusions:

  • PFAS exposure during MZT disrupts the establishment of embryonic gene regulatory networks.
  • Early developmental transitions, particularly MZT, are vulnerable to environmental contaminants.
  • PFAS exposure during MZT can lead to altered developmental patterning and organismal outcomes.