FOXE1 polymorphisms and chronic exposure to nitrates in drinking water cause metabolic dysfunction, thyroid abnormalities, and genotoxic damage in women

Gandarilla-Esparza, D.D.; Calleros-Rincón, Esperanza Yasmín; Macías, Hortensia Moreno; González-Delgado, María Fernanda; Vargas, Gonzalo García; Sustaita, Jaime Duarte; González‐Zamora, Alberto; Ríos-Sánchez, Efraín; Pérez‐Morales, Rebeca

doi:10.1590/1678-4685-gmb-2021-0020

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…The findings of the present study suggest that urine analysis of the participants who are regular consumers of soft drinks has an increased number of nitrates in urine as compared to those who do not consume soft drinks. Gandarilla-Esparza et al 16 states that chronic exposure to nitrates in water for human consumption caused metabolic and hormonal alterations and genotoxic damage in women. This finding suggests the risk of metabolic disturbances in soft drink users.…”

Section: Resultsmentioning

confidence: 99%

Soft Drinks Intake is Associated with Obesity and Urine Disorders in Medical Students

Mughal¹,

Parveen²,

Faruqi³

et al. 2022

PJMHS

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Aim: To determine the ramifications of soft drinks on Body Mass Index and effects on various renal parameters. Study design: Cross-sectional study Place and duration of study: HBS Medical and Dental College from 1st January 2020 to 31st December 2021. Methodology: One hundred and ten students from first year to final year MBBS were recruited from Medical Colleges of Islamabad. We assessed caffeinated sugar beverage consumption (Sprite, Mountain Dew, Coke, Pepsi & 7-Up). Inclusion criteria consisted of users (n=48) who took caffeinated soft drinks at least 5-7 glasses/week. Those who took less than this drink was labelled non-users (n=62). Questionnaire we used was self-administered about sociodemographic data, height, weight, soft drinks consumption frequency, and a record of urine R/E Combi 10 strip test. Results: There were 41(37.3%) males and 69(62.7%) females. The percentage of underweight, normal, overweight and obese students was 31.8%, 36.4%, 22.7% and 9.1% respectively. Out of total females (62.7%), the group overweight (30.4%) and obese (10.1%) was highly significant. (p=0.008). The user students n=48(43.6%) took caffeinated drinks more than 5-7 glasses/week and were found to be significantly obese p=0.17 as compared to non-users n=62(56.4%).Soft drink consumption was significantly associated with proteins appearance in urine (p=0.00) and leucocytes (p=0.17) and the mean PH of urine of soda users was highly significantly acidic (p=0.00) by using combi-10 test strips. Conclusion: Very high sugar contents and other ingredients in soft drinks can be associated with obesity, metabolic and kidney disturbances in young students which in chronic cases exacerbate the condition. Keywords: Obesity, Urine disorder, Caffeinated drinks

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Section: Resultsmentioning

confidence: 99%

Soft Drinks Intake is Associated with Obesity and Urine Disorders in Medical Students

Mughal¹,

Parveen²,

Faruqi³

et al. 2022

PJMHS

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“…However, research in that field of gene-environment interactions is still limited. Until now, only one interaction of FOXE1 with an environmental factor was described; two FOXE1 polymorphisms increased susceptibility to metabolic and thyroid dysfunction caused by nitrates in drinking water (Gandarilla-Esparza et al 2021). Apart from a useful model for hypothyroidism, the foxe1 mutant zebrafish also appears to be suitable for gene-environment interaction studies to craniofacial malformations.…”

Section: Discussionmentioning

confidence: 99%

foxe1mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations

Raterman,

Wagener,

Zethof

et al. 2024

Preprint

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FOXE1 mutations in humans are associated with Bamforth-Lazarus syndrome, characterized by cleft palate and hypothyroidism. Moreover, polymorphisms of FOXE1 are implicated in non- syndromic cleft palate. Much uncertainty still exists about the function of transcription factor FOXE1 in development. To address this, we have previously developed a foxe1 mutant zebrafish demonstrating mineralization defects in larvae. In the present study, we further investigate the thyroid status and skeletal phenotype of adult foxe1 mutants. Compared to wild type controls, mutant fish have increased expression of hypothalamic tshb, and hepatic dio1 and dio2. In plasma we found higher circulating Mg levels, together these findings are indicative of hypothyroidism. We further observed mineralization defects in scales, likely due to enhanced osteoclast activity as measured by increased expression levels of the markers tracp, ctsk and rankl. Gene-environment interactions in the etiology of FOXE1-related craniofacial abnormalities remain elusive, which prompts the need for models to investigate genotype-phenotype associations. We here investigated whether ethanol exposure increases the risk of developing craniofacial malformations in foxe1 mutant larvae that we compared to wild types. We found in ethanol-exposed mutants an increased incidence of developmental malformations and marked changes in gene expression patterns of cartilage markers (sox9a), apoptotic markers (casp3b), retinoic acid metabolism (cyp26c1), and tissue hypoxia markers (hifaa, hifab). Taken together, this study shows that the foxe1 mutant zebrafish recapitulates phenotypes associated with FOXE1 mutations in human patients and a clear foxe1-ethanol interaction.

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“…The expression of these three genes plays a considerable role in the proper morphogenesis of the thyroid gland and maintenance of its functionally differentiated state [ 40 ]. Specifically, FOXE1 is involved in thyroid precursor cells migration [ 41 ], while NKX2-1 and PAX8 are essential for maintaining the survival and structural integrity of thyroid cell precursors [ 42 ]. Therefore, we formulated the hypothesis that decreased expression levels of these three genes, respectively, caused by MMI and nitrate, might disrupt morphogenesis of the thyroid gland in the B. gargarizans embryos.…”

Section: Discussionmentioning

confidence: 99%

Morphological and Transcriptomic Analyses Reveal the Toxicological Mechanism and Risk of Nitrate Exposure in Bufo gargarizans Embryos

Xie,

Niu,

Xiao

et al. 2024

Animals

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In recent years, nitrate (NO3-N) pollution in water bodies has been increasing due to the excessive use of nitrogen-based fertilizers. Exposure to NO3-N during the development of amphibian embryos may have lasting effects on the growth and development of individuals and even threaten their survival, but the toxicity mechanism of NO3-N in amphibian embryos prior to thyroid morphogenesis remains unclear. In the present study, Bufo gargarizans was selected as the model organism to investigate the toxic effects of 10 mg/L and 100 mg/L NO3-N exposure (N10 and N100) on amphibian embryos using methimazole (MMI) and exogenous thyroxine (T4) as the reference groups. We found that T4, MMI, N10 and N100 inhibited B. gargarizans embryo growth and development, with MMI and N100 showing the earliest and strongest effects. Transcriptome analysis revealed that MMI and NO3-N (especially N100) significantly downregulated genes related to thyroid morphogenesis and cholesterol metabolism, while upregulating genes related to inflammation and apoptosis. Together, these results contribute to a deeper understanding of the complex mechanisms by which NO3-N disrupts B. gargarizans embryonic development, reveal the potential risks of NO3-N pollution to other aquatic organisms, and provide insights into the conservation of a broader ecosystem.

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FOXE1 polymorphisms and chronic exposure to nitrates in drinking water cause metabolic dysfunction, thyroid abnormalities, and genotoxic damage in women

Cited by 9 publications

References 31 publications

Soft Drinks Intake is Associated with Obesity and Urine Disorders in Medical Students

Soft Drinks Intake is Associated with Obesity and Urine Disorders in Medical Students

foxe1mutant zebrafish show indications of a hypothyroid phenotype and increased sensitivity to ethanol for craniofacial malformations

Morphological and Transcriptomic Analyses Reveal the Toxicological Mechanism and Risk of Nitrate Exposure in Bufo gargarizans Embryos

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