Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul;202(7):3237-3247.
doi: 10.1007/s12011-023-03916-5. Epub 2023 Oct 26.

Impact of Fluoride Exposure on Rat Placenta: Foetal/Placental Morphometric Alterations and Decreased Placental Vascular Density

Jonathan Guerrero-Arroyo  1 , Mónica I Jiménez-Córdova  1 , Octavio G Aztatzi-Aguilar  1 , Luz M Del Razo  2
Affiliations

Impact of Fluoride Exposure on Rat Placenta: Foetal/Placental Morphometric Alterations and Decreased Placental Vascular Density

Jonathan Guerrero-Arroyo et al. Biol Trace Elem Res. 2024 Jul.

Abstract

Inorganic fluoride is a geogenic and anthropogenic contaminant widely distributed in the environment and commonly identified in contaminated groundwater. There is limited information on the effect of fluoride exposure on pregnancy. The aim of this study was to evaluate possible placental alterations of fluoride exposure in a rat model simulating preconception and pregnancy exposure conditions in endemic areas. Fluoride exposure was administered orally to foetuses of dams exposed to 2.5 and 5 mg fluoride/kg/d. Foetal weight, height, foetal/placental weight ratio, placental zone thickness, levels of malondialdehyde (MDA) and vascular endothelial growth factor-A (VEGF-A) and vascular density in placental tissue were evaluated. The results showed a nonlinear relationship between these outcomes and the dose of fluoride exposure. In addition, a significant increase in the fluoride concentration in placental tissue was observed. The group that was exposed to 2.5 mg fluoride/kg/d had a greater increase in both MDA levels and VEGF-A levels than the higher dose group. A significant increase in the thickness of the placental zones and a decrease in the vascular density of the labyrinth zone area were also observed in the fluoride-exposed groups. In conclusion, the data obtained demonstrate that fluoride exposure results in morpho-structural alterations in the placenta and that non-monotonic changes in MDA, VEGF-A levels and placental foetal weight ratio were at environmentally relevant concentrations.

Keywords: Fluoride; Morphometrics; Placental abnormalities; Placental weight; Pregnancy; Vascular density.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Experimental design of rat exposure to fluoride. Wistar rats were exposed to fluoride by gastric gavage for 33 days. The administered dose was purified water, 2.5 and 5 mg fluoride/kg/d by gavage. The Pap smear was evaluated daily before mating. The presence of sperm in the Pap smear represented gestational day 1 (GD1); GD19, the delivery was performed.
Fig. 2
Fig. 2
Representative foetuses and placentas from the litter on GD 19. A Foetus and placenta of the control group; B foetus and placenta treated with 2.5 mg fluoride/kg/d; C foetus and placenta treated with 5 mg fluoride/kg/d, foetus with apparent erythema. Bar = 1 cm
Fig. 3
Fig. 3
Correlation between foetal and placental weight. a Control group; b 2.5 mg fluoride/kg/d group; c 5 mg fluoride/kg/d group
Fig. 4
Fig. 4
Malondialdehyde (MDA) concentration in placenta. Bars represent mean ± SD of MDA concentration (μM) per gram of protein; hydrogen peroxide (3% H2O2) was used as positive control for MDA test; n = 15 placentas per group, experiments were performed in triplicate; *p < 0.01 significantly different by control group (one-way ANOVA test with post hoc Tukey test)
Fig. 5
Fig. 5
Histologic micrographs of rat placenta on gestational day 19. The dotted line delimits a placental zone. a Representative staining of placental slices at 4X from the control group; b representative staining of placental slices at 10× from the control group; c representative staining of placental slices at 4× from the 2.5 mg fluoride/kg/d; d representative placenta slice staining at 10× of the 2.5 mg fluoride/kg/d group; e representative placenta slice staining at 4× of the 5 mg fluoride/kg/d group; f representative placenta slice staining at 10× of the 5 mg fluoride/kg/d group; H&E stain, BV, blood vessel; BD, basal decidua; GC, glycogenic cells; TGC, trophoblastic giant cells; BZ, basal zone; LZ, labyrinth zone
Fig. 6
Fig. 6
Impact of maternal fluoride exposure on vascular density in the labyrinthine zone area. Bars represent mean ± SD of vascular density expressed in vessels/mm2. *p < 0.0001 significantly different from the control group (one-way ANOVA test with post hoc Tukey test). #p < 0.0001 significantly different between fluoride exposure groups (one-way ANOVA test)
Fig. 7
Fig. 7
Vascular endothelial growth factor (VEGF-A) concentration in placental tissue. Bars represent mean ± SD of VEGF-A concentration expressed in pg/mg of protein. *p < 0.05 significantly different from the control group (one-way ANOVA test with post hoc Tukey test)
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Limon-Pacheco JH, Jimenez-Cordova MI, Cardenas-Gonzalez M, Sanchez Retana IM, Gonsebatt ME, Del Razo LM. Potential co-exposure to arsenic and fluoride and biomonitoring equivalents for Mexican children. Ann Glob Health. 2018;84:257–273. doi: 10.29024/aogh.913. - DOI - PMC - PubMed
    1. Podgorski J, Berg M. Global analysis and prediction of fluoride in groundwater. Nat Commun. 2022;13:4232–4241. doi: 10.1038/s41467-022-31940-x. - DOI - PMC - PubMed
    1. Cardenas-Gonzalez M, Jacobo Estrada T, Rodriguez-Munoz R, Barrera-Chimal J, Bobadilla NA, Barbier OC, Del Razo LM. Sub-chronic exposure to fluoride impacts the response to a subsequent nephrotoxic treatment with gentamicin. J Appl Toxicol. 2016;36:309–319. doi: 10.1002/jat.3186. - DOI - PubMed
    1. Jimenez-Cordova MI, Cardenas-Gonzalez M, Aguilar-Madrid G, Sanchez-Pena LC, Barrera-Hernandez A, Dominguez-Guerrero IA, Gonzalez-Horta C, Barbier OC, Del Razo LM. Evaluation of kidney injury biomarkers in an adult Mexican population environmentally exposed to fluoride and low arsenic levels. Toxicol Appl Pharmacol. 2018;352:97–106. doi: 10.1016/j.taap.2018.05.027. - DOI - PubMed
    1. Valdez Jimenez L, Lopez Guzman OD, Cervantes Flores M, Costilla-Salazar R, Calderon Hernandez J, Alcaraz Contreras Y, Rocha-Amador DO. In utero exposure to fluoride and cognitive development delay in infants. Neurotoxicol. 2017;59:65–70. doi: 10.1016/j.neuro.2016.12.011. - DOI - PubMed

LinkOut - more resources

-