Differential expression and immunoreactivity of thyroid hormone transporters MCT8 and OATP1C1 in rat ovary

Luis, Enoch; Fernández, Yesenia; Alvarado, Mayvi; Juárez-Santacruz, Libertad; García-Nieto, Edelmira; Anaya-Hernández, Arely

doi:10.1016/j.acthis.2019.151440

Acta Histochemica

2019

DOI: 10.1016/j.acthis.2019.151440

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Differential expression and immunoreactivity of thyroid hormone transporters MCT8 and OATP1C1 in rat ovary

Enoch Luis

Yesenia Fernández

Mayvi Alvarado

et al.

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2024

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Cited by 2 publications

References 56 publications

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Non-targeted metabolomics revealed novel links between serum metabolites and primary ovarian insufficiency: a Mendelian randomization study

Chen,

Zhou,

Zhou

et al. 2024

Front. Endocrinol.

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BackgroundPrimary ovarian insufficiency (POI) is a common clinical endocrine disorder with a high heterogeneity in both endocrine hormones and etiological phenotypes. However, the etiology of POI remains unclear. Herein, we unraveled the causality of genetically determined metabolites (GDMs) on POI through Mendelian randomization (MR) study with the overarching goal of disclosing underlying mechanisms.MethodsGenetic links with 486 metabolites were retrieved from GWAS data of 7824 European participants as exposures, while GWAS data concerning POI were utilized as the outcome. Via MR analysis, we selected inverse-variance weighted (IVW) method for primary analysis and several additional MR methods (MR-Egger, weighted median, and MR-PRESSO) for sensitivity analyses. MR-Egger intercept and Cochran’s Q statistical analysis were conducted to assess potential heterogeneity and pleiotropy. In addition, genetic variations in the key target metabolite were scrutinized further. We conducted replication, meta-analysis, and linkage disequilibrium score regression (LDSC) to reinforce our findings. The MR Steiger test and reverse MR analysis were utilized to assess the robustness of genetic directionality. Furthermore, to deeply explore causality, we performed colocalization analysis and metabolic pathway analysis.ResultsVia IVW methods, our study identified 33 metabolites that might exert a causal effect on POI development. X-11437 showed a robustly significant relationship with POI in four MR analysis methods (PIVW=0.0119; Pweighted-median =0.0145; PMR-Egger =0.0499; PMR-PRESSO =0.0248). Among the identified metabolites, N-acetylalanine emerged as the most significant in the primary MR analysis using IVW method, reinforcing its pivotal status as a serum biomarker indicative of an elevated POI risk with the most notable P-value (PIVW=0.0007; PMR-PRESSO =0.0022). Multiple analyses were implemented to further demonstrate the reliability and stability of our deduction of causality. Reverse MR analysis did not provide evidence for the causal effects of POI on 33 metabolites. Colocalization analysis revealed that some causal associations between metabolites and POI might be driven by shared genetic variants.ConclusionBy incorporating genomics with metabolomics, this study sought to offer a comprehensive analysis in causal impact of serum metabolome phenotypes on risks of POI with implications for underlying mechanisms, disease screening and prevention.

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Non-targeted metabolomics revealed novel links between serum metabolites and primary ovarian insufficiency: a Mendelian randomization study

Chen,

Zhou,

Zhou

et al. 2024

Front. Endocrinol.

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Altered Expression of Thyroid- and Calcium Ion Channels-Related Genes in Rat Testes by Short-Term Exposure to Commercial Herbicides Paraquat or 2,4-D

Luis,

Conde-Maldonado,

García-Nieto

et al. 2024

JoX

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Exposure to pesticides such as paraquat and 2,4-dichlorophenoxyacetic acid (2,4-D) has been linked to harmful health effects, including alterations in male reproduction. Both herbicides are widely used in developing countries and have been associated with reproductive alterations, such as disruption of spermatogenesis and steroidogenesis. The thyroid axis and Ca2+-permeable ion channels play a key role in these processes, and their disruption can lead to reproductive issues and even infertility. This study evaluated the short-term effects of exposure to commercial herbicides based on paraquat and 2,4-D on gene expression in rat testes. At the molecular level, exposure to paraquat increased the expression of the thyroid hormone transporters monocarboxylate transporter 8 (Mct8) and organic anion-transporting polypeptide 1C1 (Oatp1c1) and the thyroid receptor alpha (TRα), suggesting a possible endocrine disruption. However, it did not alter the expression of the sperm-associated cation channels (CatSper1-2) or vanilloid receptor-related osmotically activated channel (Trpv4) related to sperm motility. In contrast, exposure to 2,4-D reduced the expression of the Mct10 transporter, Dio2 deiodinase, and CatSper1, which could affect both the availability of T3 in testicular cells and sperm quality, consistent with previous studies. However, 2,4-D did not affect the expression of CatSper2 or Trpv4. Deregulation of gene expression could explain the alterations in male reproductive processes reported by exposure to paraquat and 2,4-D. These thyroid hormone-related genes can serve as molecular biomarkers to assess endocrine disruption due to exposure to these herbicides, aiding in evaluating the health risks of pesticides.

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Differential expression and immunoreactivity of thyroid hormone transporters MCT8 and OATP1C1 in rat ovary

Cited by 2 publications

References 56 publications

Non-targeted metabolomics revealed novel links between serum metabolites and primary ovarian insufficiency: a Mendelian randomization study

Non-targeted metabolomics revealed novel links between serum metabolites and primary ovarian insufficiency: a Mendelian randomization study

Altered Expression of Thyroid- and Calcium Ion Channels-Related Genes in Rat Testes by Short-Term Exposure to Commercial Herbicides Paraquat or 2,4-D

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