Methimazole-induced hypothyroidism disrupts testicular glycogen regulation without affecting insulin expression or signaling in rats Roberta da Fonseca Coutinho Pontes, Juliana Santos Romão, Nathalia Pereira de Farias da Silva, Manuela Farias Joppert, Ana Clara Chagas Coutinho Pontes, Lorena Cristina Souza e Souza, Cherley Borba Vieira Andrade, Veronica Aiceles, José Antônio Silva Ribas, Karen Jesus Oliveira Molecular and Cellular Endocrinology, 2026 Thyroid hormones (TH) are essential regulators of energy metabolism and reproductive function. Hypothyroidism is a highly prevalent endocrine disorder and a risk factor for male infertility; however, its effects on the molecular pathways regulating testicular energy metabolism remains poorly understood. This study investigated the impact of hypothyroidism on insulin expression, insulin signaling, and glycogen regulation in the testis. Male Wistar rats were divided into control (CT) and hypothyroid (Hypo) groups, with hypothyroidism induced by methimazole (0.03%) in the drinking water for 21 days. Testicular mRNA expression of insulin and glucose transporters were evaluated by qPCR, while proteins related to insulin signaling, glucose metabolism, and glycophagy were analyzed by Western blot. Testicular insulin content was assessed by immunohistochemistry. Hypothyroidism reduced testosterone levels, decreased testicular mass, and impaired sperm parameters. It increased insulin receptor total protein levels and phosphorylation, without changes in the phospho/total ratio, while IRS-1, p-IRS1, AKT, p-AKT, and PTP-1B remained unchanged. Slc2a1 expression was upregulated and Slc2a3 downregulated, indicating adaptative changes in glucose uptake. Protein levels of AMPK, p-AMPK, GSK-3β, and p-GSK-3β remained unchanged. Increased total and phosphorylated GYS levels were observed without changes in the phospho/total ratio, suggesting potential modulation of glycogen metabolism. Although expression of the glycogen-binding protein STBD1 was increased, reduced GABARAPL1 levels suggest impaired glycophagy, consistent with unchanged testicular glycogen content observed in the hypothyroid group. Furthermore, testicular insulin expression remained unaffected. These findings suggest that hypothyroidism-induced testicular dysfunction is not primarily driven by local insulin resistance but may involve impaired glycogen mobilization via glycophagy. • Hypothyroidism increases testicular insulin receptor expression and phosphorylation • Downstream insulin signaling (IRS-1/AKT) is preserved in hypothyroid testes • Hypothyroidism alters glucose transporter expression, suggesting adaptive glucose uptake • Increased GYS phosphorylation suggests impaired glycogen synthesis in the testis • Reduced GABARAPL1 indicates defective glycophagy-mediated glycogen mobilization
Gestational fish oil supplementation in a high-fat diet induces sex-specific myokine changes in weanling offspring Juliana Woyames, Isabela De Lima Martins, Manuella Soares De Souza, Bruna Braga Saggioro, Cissa Bastos Ribeiro Da Silva, Maria Catarina Alonso Tatagiba, Rafaela Nascimento De Sousa, Cherley Borba Vieira De Andrade, Jessika Geisebel Oliveira Neto, Mariana Macedo De Almeida, Isis Hara Trevenzoli, Carmen Cabanelas Pazos Moura Journal of Endocrinology, 2025 Previous research showed that a maternal high-fat (HF) diet during the perinatal period impairs skeletal muscle metabolism in offspring. Supplementing the HF diet with fish oil (FO), a source of n-3 polyunsaturated fatty acids, during gestation partially mitigates these adverse effects at weaning. This study investigated whether maternal HF diet, with or without FO supplementation during gestation, alters the expression of muscle-secreted molecules (myokines) in female and male offspring at weaning. Female Wistar rats were fed a control (9% lipids) or HF diet (29% lipids) for 8 weeks before mating and throughout gestation and lactation. A subset of HF-fed dams received a 3% FO-supplemented HF diet (HFFO) during gestation. In glycolytic extensor digitorum longus (EDL) muscle, FO tended to decrease Nmb (neuromedin B) mRNA in females and increased Erfe (myonectin) mRNA in males, compared to sex-matched HF groups. HFFO males also exhibited elevated expression of genes involved in fatty acid uptake and oxidation, suggesting enhanced lipid metabolism. However, FO did not reverse the HF-induced downregulation of Igf1r in EDL or Igf1 in the oxidative soleus muscle of male offspring, and muscle fiber size remained unchanged across groups. In the soleus muscle, FO increased Il6 mRNA in females, while in males, FO induced FNDC5 (the irisin precursor), accompanied by increased uncoupling protein-1 in subcutaneous white adipose tissue, suggesting increased thermogenic activity. Gestational FO supplementation induces sex- and muscle-specific alterations in myokine expression in weanling offspring exposed to a maternal HF diet, potentially shaping early muscle metabolism and contributing to sex-dependent metabolic programming.
Prenatal Exposure to Herbicide 2,4-Dichlorophenoxyacetic Acid (2,4D) Exacerbates Zika Virus Neurotoxicity In Vitro and In Vivo Raissa Rilo Christoff, Débora Santos da Silva, Rafael Ferreira Lima, Ana Luiza Meneguci Moreira Franco, Luiza Mendonça Higa, Átila Duque Rossi, Carolina Batista, Cherley Borba Vieira de Andrade, Tania Maria Ortiga‐Carvalho, Lucas Ascari, Bárbara de Azevedo Abrahim‐Vieira, Maria Bellio, Amilcar Tanuri, Flavia Martinez de Carvalho, Patricia Pestana Garcez, Flavio Alves Lara Environmental Toxicology, 2025 Zika virus (ZIKV) infection during pregnancy can lead to a set of congenital malformations known as Congenital ZIKV syndrome (CZS), whose main feature is microcephaly. The geographic distribution of CZS in Brazil during the 2015–2017 outbreak was asymmetrical, with a higher prevalence in the Northeast and Central‐West regions of the country, despite the ubiquitous distribution of the vector Aedes aegypti, indicating that environmental factors could influence ZIKV vertical transmission and/or severity. Here we investigate the involvement of the most used agrochemicals in Brazil with CZS. First, we exposed human neuroblastoma SK‐N‐AS cells to the 15 frequently used agrochemical molecules or derivative metabolites able to cross the blood–brain barrier. We found that a derived metabolite from a widely used herbicide in the Central‐West region, 2,4‐dichlorophenoxyacetic acid (2,4D), exacerbates ZIKV neurotoxic effects in vitro. We validate this observation by demonstrating vertical transmission leading to microcephaly in the offspring of immunocompetent C57BL/6J mice exposed to water contaminated with 0.025 mg/L of 2,4D. Newborn mice whose dams were exposed to 2,4D and infected with ZIKV presented a smaller brain area and cortical plate size compared to the control. Also, embryos from animals facing the co‐insult of ZIKV and 2,4D exposition presented higher Caspase 3 positive cells in the cortex, fewer CTIP2+ neurons and proliferative cells at the ventricular zone, and a higher viral load. This phenotype is followed by placental alterations, such as vessel congestion, and apoptosis in the labyrinth and decidua. We also observed a mild spatial correlation between CZS prevalence and 2,4D use in Brazil's North and Central‐West regions, with R2 = 0.4 and 0.46, respectively. Our results suggest that 2,4D exposition facilitates maternal vertical transmission of ZIKV, exacerbating CZS, possibly contributing to the high prevalence of this syndrome in Brazil's Central‐West region compared to other regions.
Aging promotes an increase in mitochondrial fragmentation in astrocytes Ana Paula Bergamo Araujo, Gabriele Vargas, Lívia de Sá Hayashide, Isadora Matias, Cherley Borba Vieira Andrade, Jorge José de Carvalho, Flávia Carvalho Alcantara Gomes, Luan Pereira Diniz Frontiers in Cellular Neuroscience, 2024 IntroductionBrain aging involves a complex interplay of cellular and molecular changes, including metabolic alterations and the accumulation of senescent cells. These changes frequently manifest as dysregulation in glucose metabolism and mitochondrial function, leading to reduced energy production, increased oxidative stress, and mitochondrial dysfunction—key contributors to age-related neurodegenerative diseases.MethodsWe conducted experiments on two models: young (3–4 months) and aged (over 18 months) mice, as well as cultures of senescent and control mouse astrocytes. Mitochondrial content and biogenesis were analyzed in astrocytes and neurons from aged and young animals. Cultured senescent astrocytes were examined for mitochondrial membrane potential and fragmentation. Quantitative PCR (qPCR) and immunocytochemistry were used to measure fusion- and fission-related protein levels. Additionally, transmission electron microscopy provided morphological data on mitochondria.ResultsAstrocytes and neurons from aged animals showed a significant reduction in mitochondrial content and a decrease in mitochondrial biogenesis. Senescent astrocytes in culture exhibited lower mitochondrial membrane potential and increased mitochondrial fragmentation. qPCR and immunocytochemistry analyses revealed a 68% increase in fusion-related proteins (mitofusin 1 and 2) and a 10-fold rise in DRP1, a key regulator of mitochondrial fission. Transmission electron microscopy showed reduced perimeter, area, and length-to-diameter ratio of mitochondria in astrocytes from aged mice, supported by elevated DRP1 phosphorylation in astrocytes of the cerebral cortex.DiscussionOur findings provide novel evidence of increased mitochondrial fragmentation in astrocytes from aged animals. This study sheds light on mechanisms of astrocytic metabolic dysfunction and mitochondrial dysregulation in brain aging, highlighting mitochondrial fragmentation as a potential target for therapeutic interventions in age-related neurodegenerative diseases.
Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High-Fat Diet Jessika Geisebel Oliveira Neto, Juliana Woyames, Cherley Borba Vieira Andrade, Mariana Macedo de Almeida, Larissa Brito Fassarella, Georgia Correia Atella, Christina Maeda Takyia, Isis Hara Trevenzoli, Carmen Cabanelas Pazos‐Moura Molecular Nutrition and Food Research, 2023 ScopePerinatal maternal moderately high‐fat diet (mHFD) is associated with obesity and fatty liver disease in offspring, and maternal fish oil (FO: n‐3 PUFA source) supplementation may attenuate these disorders. This study evaluates the effects of FO given to pregnant rats fed a mHFD on the offspring's liver at weaning.Methods and resultsFemale Wistar rats receive an isoenergetic, control (CT: 10.9% from fat) or high‐fat (HF: 28.7% from fat) diet before mating, and throughout pregnancy and lactation. FO supplementation (HFFO: 2.9% of FO in the HF diet) is given to one subgroup of HF dams during pregnancy. At weaning, male and female mHFD offspring display higher body mass, adiposity, and hepatic cellular damage, steatosis, and inflammation, accompanied by increased damaged mitochondria. FO does not protect pups from systemic metabolic alterations and partially mitigates hepatic histological damage induced by mHFD only in females. However, FO reduces mRNA expression of lipogenic genes, and mitochondrial damage, and modified mitochondrial morphology suggestive of early adaptations via mitochondrial dynamics.ConclusionsGestational FO supplementation has limited beneficial effects on the damage caused by perinatal mHFD consumption in offspring's liver at weaning. However, FO imprinting effect on lipid metabolism and mitochondria may have beneficial long‐term outcomes.
Cirrhotic Liver Sustains In Situ Regeneration of Acellular Liver Scaffolds after Transplantation into G-CSF-Treated Animals Marlon Lemos Dias, Inês Julia Ribas Wajsenzon, Gabriel Bastos Naves Alves, Bruno Andrade Paranhos, Cherley Borba Vieira Andrade, Victoria Regina Siqueira Monteiro, Raysa Maria Reis de Sousa, Evelyn Nunes Goulart da Silva Pereira, Karine Lino Rodrigues, Anissa Daliry, Debora Bastos Mello, Regina Coeli dos Santos Goldenberg Cells, 2023 Acellular liver scaffolds (ALS) produced by decellularization have been successfully explored for distinct regenerative purposes. To date, it is unknown whether transplanted ALSs are affected by cirrhotic livers, either becoming cirrhotic themselves or instead remaining as a robust template for healthy cell growth after transplantation into cirrhotic rats. Moreover, little is known about the clinical course of recipient cirrhotic livers after ALS transplantation. To address these questions, we transplanted ALSs into cirrhotic rats previously treated with the granulocyte colony-stimulating factor. Here, we report successful cellular engraftment within the transplanted ALSs at 7, 15, and 30 days after transplantation. Recellularization was orchestrated by liver tissue cell activation, resident hepatocytes and bile duct proliferation, and an immune response mediated by the granulocyte components. Furthermore, we showed that transplanted ALSs ensured a pro-regenerative and anti-inflammatory microenvironment, attracted vessels from the host cirrhotic tissue, and promoted progenitor cell recruitment. ALS transplantation induced cirrhotic liver regeneration and extracellular matrix remodeling. Moreover, the transplanted ALS sustained blood circulation and attenuated alterations in the ultrasonographic and biochemical parameters in cirrhotic rats. Taken together, our results confirm that transplanted ALSs are not affected by cirrhotic livers and remain a robust template for healthy cell growth and stimulated cirrhotic liver regeneration.
Yerba mate consumption by ovariectomized rats alters white adipose tissue Victor Machado de Mello Andrade, Amanda Fernandes de Moura, Katlen da Costa Chaves, Camilla Pereira Dias da Rocha, Cherley Borba Vieira de Andrade, Isis Hara Trevenzoli, Tania Maria Ortiga-Carvalho, Luciane Cláudia Barcellos, Mário Vaisman, Verônica Pinto Salerno Molecular and Cellular Endocrinology, 2023
Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice Isalira Peroba Rezende Ramos, Marlon Lemos Dias, Alan Cesar Nunes De Moraes, Fernanda Guimarães Meireles Ferreira, Sergio Augusto Lopes Souza, Bianca Gutfilen, Thiago Barboza, Cibele Ferreira Pimentel, Cintia Marina Paz Batista, Tais Hanae Kasai-Brunswick, Fabio Da Silva De Azevedo Fortes, Cherley Borba Vieira De Andrade, Regina Coeli dos Santos Goldenberg Frontiers in Pharmacology, 2021
Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology Thamires Siqueira Oliveira, Anderson Teixeira Santos, Cherley Borba Vieira Andrade, Johnatas Dutra Silva, Natália Blanco, Nazareth de Novaes Rocha, Juliana Woyames, Pedro Leme Silva, Patricia Rieken Macedo Rocco, Wagner Seixas da-Silva, Tânia Maria Ortiga-Carvalho, Flavia Fonseca Bloise Frontiers in Physiology, 2021
Effect of Sublethal Prenatal Endotoxaemia on Murine Placental Transport Systems and Lipid Homeostasis Mila W. Reginatto, Klaus Novaes Fontes, Victoria R. S. Monteiro, Natalia L. Silva, Cherley Borba Vieira Andrade, Hanailly Ribeiro Gomes, Guinever E. Imperio, Flavia Fonseca Bloise, George Eduardo Gabriel Kluck, Georgia Correa Atella, Stephen G. Matthews, Enrrico Bloise, Tania M. Ortiga-Carvalho Frontiers in Microbiology, 2021
ZIKV Disrupts Placental Ultrastructure and Drug Transporter Expression in Mice Cherley Borba Vieira Andrade, Victoria Regina de Siqueira Monteiro, Sharton Vinicius Antunes Coelho, Hanailly Ribeiro Gomes, Ronny Paiva Campos Sousa, Veronica Muller de Oliveira Nascimento, Flavia Fonseca Bloise, Stephen Giles Matthews, Enrrico Bloise, Luciana Barros Arruda, Tania Maria Ortiga-Carvalho Frontiers in Immunology, 2021
Resveratrol promotes liver regeneration in drug-induced liver disease in mice Alan Cesar Nunes de Moraes, Cherley Borba Vieira de Andrade, Isalira Peroba Rezende Ramos, Marlon Lemos Dias, Cintia Marina Paz Batista, Cibele Ferreira Pimentel, Jorge Jose de Carvalho, Regina Coeli dos Santos Goldenberg Food Research International, 2021
Thyroid redox imbalance in adult Wistar rats that were exposed to nicotine during breastfeeding Rosiane Aparecida Miranda, Egberto Gaspar de Moura, Patrícia Novaes Soares, Thamara Cherem Peixoto, Bruna Pereira Lopes, Cherley Borba Vieira de Andrade, Elaine de Oliveira, Alex C. Manhães, Caroline Coelho de Faria, Rodrigo Soares Fortunato, Patricia Cristina Lisboa Scientific Reports, 2020
Human Menstrual Blood-Derived Mesenchymal Cells Improve Mouse Embryonic Development Marianna Ferreira Gonçalves, Karina Dutra Asensi, Anna Luiza Lima Nascimento, Julia Helena Oliveira de Barros, Rosana de Almeida Santos, Cherley Borba Vieira de Andrade, Tais Hanae Kasai-Brunswick, Marcel Frajblat, Tania M. Ortiga-Carvalho, Regina Coeli dos Santos Goldenberg Tissue Engineering Part A, 2020
Sepsis Impairs Thyroid Hormone Signaling and Mitochondrial Function in the Mouse Diaphragm Flavia Fonseca Bloise, Anderson Teixeira Santos, Juliana de Brito, Cherley Borba Vieira de Andrade, Thamires Siqueira Oliveira, Aline Fonseca Pereira de Souza, Klaus Novaes Fontes, Johnatas D Silva, Natália Blanco, Pedro Leme Silva, Patricia Rieken Macedo Rocco, Eric Fliers, Anita Boelen, Wagner Seixas da-Silva, Tânia Maria Ortiga-Carvalho Thyroid, 2020
Aliskiren reduces the adrenal zona glomerulosa apoptosis and autophagy in Wistar rats with 2K1C hypertension Veronica S. de Matos, Ana L. R. do Nascimento, Priscila G. Pereira, Kíssila Rabelo, Cherley B. V. Andrade, Alan C. N. Moraes, Camila Salata, Victor H. V. de O. Araújo, Bianca Torres Ciambarella, Aline Bonfim Vieira, Luciana Lontro Alves, Jemima F. R. da Silva, Jorge J. de Carvalho International Journal of Hypertension, 2020
Zika virus impairs the development of blood vessels in a mouse model of congenital infection P. P. Garcez, H. B. Stolp, S. Sravanam, R. R. Christoff, J. C. C. G. Ferreira, A. A. Dias, P. Pezzuto, L. M. Higa, J. Barbeito-Andrés, R. O. Ferreira, C. B V. Andrade, M. Siqueira, T. M. P. Santos, J. Drumond, A. Hoerder-Suabedissen, C. V. F. de Lima, F. Tovar-Moll, R. T. Lopes, L. Fragel-Madeira, R. Lent, T. M. Ortiga-Carvalho, J. Stipursky, M. Bellio, A. Tanuri, Z. Molnár Scientific Reports, 2018
Radiotherapy-induced skin reactions induce fibrosis mediated by TGF-β1 cytokine Cherley Borba Vieira de Andrade, Isalira Peroba Rezende Ramos, Alan César Nunes de Moraes, Ana Lúcia Rosa do Nascimento, Camila Salata, Regina Coeli dos Santos Goldenberg, Jorge José de Carvalho, Carlos Eduardo Veloso de Almeida Dose Response, 2017
Analysis of femur head microstructure in ovariectomized rats C B V Andrade, L P Nogueira, C Salata, C M da Silva, S C Ferreira-Machado, C E de Almeida, A P Almeida, M V Colaço, R C P V Alessio, D Braz, G Tromba, R C Barroso Journal of Instrumentation, 2013
Caspase-3 activation and increased procollagen type I in irradiated hearts Samara C. Ferreira-Machado, Camila Salata, Nazareth N. Rocha, Alexandre F.S. Corrêa, Suzana Côrte-Real, Antônio A.F. Peregrino, Vera M.A. de Campos, Cherley B.V. Andrade, Mario Bernardo-Filho, Januário B. Cabral-Neto, Carlos E. Dealmeida Anais Da Academia Brasileira De Ciencias, 2013
