Investigating the Effects of Exposure to PFOA During Pregnancy on the Expression of Neurotrophin 3 (NT3) and Neurotrophin 4 (NT4) Factors in the Brain of Newborn Rats

Document Type : Original Article(s)

Authors

1 MSc Student, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Previous studies have shown perfluorooctanoic acid (PFOA) causes organ cytotoxicity. There are high levels of PFOA in cord blood that may affect organogenesis. In the present study, the effects of exposure to perfluorooctanoic acid (PFOA) during pregnancy were investigated on the expression of neurotrophin 3 (NT3) and neurotrophin 4 (NT4) factors in the rat brain.
Methods: In this study, the newborns brains of 35 pregnant Wistar rats were used. Wistar rats were randomly divided into five groups, including control groups, sham groups, and three groups receiving PFOA at the rate of 1, 5, and 10 mg per kilogram of body weight, were used. In the group receiving PFOA, this compound was given daily using the gavage technique. Using ELISA and Real-Time PCR methods, we investigated the expression of NT3 and NT4 factors in the brain of newborn mice 20 days after birth.
Findings: The results showed that the average expression of NT3 and NT4 genes and proteins in the PFOA receiving groups, especially in the 5 and 10 mg PFOA groups, significantly increased compared to other groups (P ≤ 0.001).
Conclusion: The results of the present study showed that exposure to PFOA during pregnancy can lead to increased expression of NT3 and NT4 factors. Increasing these factors by suppressing the oxidant and apoptotic effects of PFOA can prevent PFOA-induced neurological disorders.

Highlights

Zeinolabedin Sharifian Dastjerdi: Google Scholar, PubMed

Nazem Ghasemi: Google Scholar, PubMed

Keywords

Main Subjects


  1. Li D, Zhang L, Zhang Y, Guan S, Gong X, Wang X. Maternal exposure to perfluorooctanoic acid (PFOA) causes liver toxicity through PPAR-α pathway and lowered histone acetylation in female offspring mice. Environ Sci Pollut Res Int 2019; 26(18): 18866-75.
  2. Neisiani AK, Mousavi MK, Soltani M, Aliomrani M. Perfluorooctanoic acid exposure and its neurodegenerative consequences in C57BL6/J mice. Naunyn Schmiedebergs Arch Pharmacol 2023; 396(10): 2357-67.
  3. Fragki S, Dirven H, Fletcher T, Grasl-Kraupp B, Bjerve Gützkow K, Hoogenboom R, et al. Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?. Crit Rev Toxicol 2021; 51(2): 141-64.
  4. Kerger BD, Copeland TL, DeCaprio AP. Tenuous dose-response correlations for common disease states: case study of cholesterol and perfluorooctanoate/sulfonate (PFOA/PFOS) in the C8 Health Project. Drug Chem Toxicol 2011; 34(4): 396-404.
  5. Steenland K, Tinker S, Frisbee S, Ducatman A, Vaccarino V. Association of perfluorooctanoic acid and perfluorooctane sulfonate with serum lipids among adults living near a chemical plant. Am J Epidemiol 2009; 170(10): 1268-78.
  6. Johansson N, Fredriksson A, Eriksson P. Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice. Neurotoxicology 2008; 29(1): 160-9.
  7. Wang Y, Mandelkow E. Tau in physiology and pathology. Nat Rev Neurosci 2016; 17(1): 5-21.
  8. Shafiei SS, Guerrero-Muñoz MJ, Castillo-Carranza DL. Tau oligomers: cytotoxicity, propagation, and mitochondrial damage. Front Aging Neurosci 2017; 9: 83.
  9. Jiang Z, Hu Z, Zeng L, Lu W, Zhang H, Li T, et al. The role of the Golgi apparatus in oxidative stress: is this organelle less significant than mitochondria? Free Radic Biol Med 2011; 50(8): 907-17.
  10. Chen Y, Zhou L, Xu J, Zhang L, Li M, Xie X, et al. Maternal exposure to perfluorooctanoic acid inhibits luteal function via oxidative stress and apoptosis in pregnant mice. Reprod Toxicol 2017; 69: 159-66.
  11. de Miranda AS, de Barros JLVM, Teixeira AL. Is neurotrophin-3 (NT-3): a potential therapeutic target for depression and anxiety?. Expert Opin Ther Targets 2020; 24(12): 1225-38.
  12. Bothwell MN. NGF, BDNF, NT3, and NT4. Handb Exp Pharmacol 2014: 220: 3-15.
  13. Ghosouri S, Soleimani M, Bakhtiari M, Ghasemi N. Evaluation of in vivo lithium chloride effects as a GSK3-β inhibitor on human adipose derived stem cells differentiation into oligodendrocytes and re-myelination in an animal model of multiple sclerosis. Mol Biol Rep 2023; 50(2): 1617-25.
  14. Gao K, Zhuang T, Liu X, Fu J, Zhang J, Fu J, et al. Prenatal exposure to per-and polyfluoroalkyl substances (PFASs) and association between the placental transfer efficiencies and dissociation constant of serum proteins–PFAS complexes. Environ Sci Technol 2019; 53(11): 6529-38.
  15. Kim S, Choi K, Ji K, Seo J, Kho Y, Park J, et al. Trans-placental transfer of thirteen perfluorinated compounds and relations with fetal thyroid hormones. Environ Sci Technol 2011; 45(17): 7465-72.
  16. Lien GW, Huang CC, Shiu JS, Chen MH, Hsieh WS, Guo YL, et al. Perfluoroalkyl substances in cord blood and attention deficit/hyperactivity disorder symptoms in seven-year-old children. Chemosphere 2016; 156: 118-27.
  17. Geiger SD, Yao P, Vaughn MG, Qian Z. PFAS exposure and overweight/obesity among children in a nationally representative sample. Chemosphere 2021; 268: 128852.