Parental Preconception and Pre-Hatch Exposure to a Developmental Insult Alters Offspring's Gene Expression and Epigenetic Regulations: An Avian Model

Int J Mol Sci. 2023 Mar 6;24(5):5047. doi: 10.3390/ijms24055047.

Abstract

Parental exposure to insults was initially considered safe if stopped before conception. In the present investigation, paternal or maternal preconception exposure to the neuroteratogen chlorpyrifos was investigated in a well-controlled avian model (Fayoumi) and compared to pre-hatch exposure focusing on molecular alterations. The investigation included the analysis of several neurogenesis, neurotransmission, epigenetic and microRNA genes. A significant decrease in the vesicular acetylcholine transporter (SLC18A3) expression was detected in the female offspring in the three investigated models: paternal (57.7%, p < 0.05), maternal (36%, p < 0.05) and pre-hatch (35.6%, p < 0.05). Paternal exposure to chlorpyrifos also led to a significant increase in brain-derived neurotrophic factor (BDNF) gene expression mainly in the female offspring (27.6%, p < 0.005), while its targeting microRNA, miR-10a, was similarly decreased in both female (50.5%, p < 0.05) and male (56%, p < 0.05) offspring. Doublecortin's (DCX) targeting microRNA, miR-29a, was decreased in the offspring after maternal preconception exposure to chlorpyrifos (39.8%, p < 0.05). Finally, pre-hatch exposure to chlorpyrifos led to a significant increase in protein kinase C beta (PKCß; 44.1%, p < 0.05), methyl-CpG-binding domain protein 2 (MBD2; 44%, p < 0.01) and 3 (MBD3; 33%, p < 0.05) genes expression in the offspring. Although extensive studies are required to establish a mechanism-phenotype relationship, it should be noted that the current investigation does not include phenotype assessment in the offspring.

Keywords: avian model; chlorpyrifos; epigenetic regulation; gene expression; neurogenesis and neurotransmission; parental preconception exposure.

MeSH terms

  • Animals
  • Birds
  • Chlorpyrifos*
  • DNA-Binding Proteins
  • Epigenesis, Genetic*
  • Female
  • Gene Expression
  • Male
  • MicroRNAs*
  • Paternal Exposure

Substances

  • Chlorpyrifos
  • DNA-Binding Proteins
  • MicroRNAs

Grants and funding