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Morphological changes in the fetal kidney induced by exposure to fluoride during pregnancy.
| Environmental Toxicology and Pharmacology | Montañez-Rodriguez E, Avila-Rojas SH, Jimenez-Dorantes AG, León-Contreras JC, Hernandez-Pando R, Arreola-Guerra JM, Gerarduzzi C, Meléndez-Camargo ME, Del Razo LM, Barbier OC. | 110:104545.
Fetal Toxicity Pregnancy Kidney Animal Study
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Abstract

Highlights

  • Fluoride (F–) is distributed to the amniotic fluid and the fetus.
  • Exposure to F– causes low weight and fetal restriction on day 20 of gestation.
  • F- decreases amniotic fluid’s creatinine concentration, osmolarity, and volume.
  • F– alters kidney development through oligonephronia.
  • Exposure to F– promotes early tubular maturation in remaining nephrons.

To determine if fluoride’s established negative impact on adult kidney health begins during gestation, an intergenerational model of Wistar rats was exposed to two doses of fluoride (2.5 or 5.0 mg/kg/day via gavage) 20 days before mating and during gestation (20 days). The results revealed that fluoride was distributed to the amniotic fluid and fetus, resulting in lower weight, more pronounced fetal restriction, and decreased creatinine, osmolarity, and amniotic fluid volume. At the kidney level, less development in the nephrogenic and cortical zones was observed in the fluoride treatment groups, with an imbalance in the number of glomeruli and “S” shaped bodies, an increase in the immunoexpression of the marker of proliferation Ki-67 in the nephrogenic zone, an increase in the expression of Wnt4 and more maturation of the renal tubules, indicating that fluoride exposure during pregnancy alters kidney development and promotes early maturation of tubular segments.

Graphical Abstract

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EXCERPT

5. Conclusions

Intergenerational exposure to F– promotes fetal restriction, which affects fetal weight and renal development. Although exposure to F– reduces the number of glomeruli, these structures and tubules significantly mature, likely indicating a compensatory mechanism.

Oligonephronia and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), in general, can have significant public health implications, particularly when they affect children, such as an increased risk of developing AKI or CKD later in life. The reduced number of nephrons leads to hyperfiltration of the remaining nephrons, leading to glomerulosclerosis, further nephron loss, and, ultimately, CKD.

The findings presented in this study have major implications for public health and for understanding the impact of environmental risk factors on the increasing incidence of pediatric and adult CKD in some areas of the world, with implications for the quality of life of those affected and for healthcare systems, and call for targeted early intervention strategies to prevent or delay the onset of more kidney-related severe complications, including monitoring of environmental pollutant exposures in the population.

Full-text article online at https://www.sciencedirect.com/science/article/pii/S1382668924001856?via%3Dihub