Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA138871 | ENA |
REPOSITORIES: ENA
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Project description:Akt1 plays a protective role in the postnatal C57BL6 mouse testis following lactational exposure to the neonatal goitrogen, propylthiouracil (PTU). To elucidate the transcriptional profile mediating this phenotypic effect, we monitored changes in testicular gene expression at postnatal days (PNDs) 15 and 25 in Akt1+/+, Akt1+/-, and Akt1-/- testes following exposure to 0.01% PTU allowing us to determine changes in gene expression due to 1.) genotype effects; 2.) exposure effects; and 3.) genotype-by-exposure interactions. Early PTU-dependent gene changes included genes involved in lipid metabolism, spermatid differentiation, meiosis and adhesion. Early Akt1-dependent effects were associated with germ cell development, spermatid development and differentiation, and sperm motility. By PND25, the Akt1 gene-environment interaction had pronounced effects on genes associated with Sertoli cell (SC) differentiation and claudin-associated junctional formation suggesting delayed formation of the blood-testis barrier (BTB). To confirm these observations, biotin tracer experiments demonstrated a permeable blood-testis barrier in PTU-exposed PKBalpha/Akt1-/- tubules as late as PND25 compared to PTU-exposed Akt1+/+ seminiferous tubules. Transmission electron microscopy demonstrated altered SC morphology, aberrant SC localization, and disorganized actin bundle formation. Taken together, loss of Akt1 coupled with postnatal exposure to the neonatal goitrogen, PTU, in the testis contributes to a transcriptional profile associated with impaired integrity of the blood-testis barrier. In summary, the Akt1-/- mouse represents a potentially important model to study BTB formation and reassembly in response to male reproductive toxicants and the various signaling networks which mediate these responses.
2011-09-04 | GSE28664 | GEO
Project description:Akt1 plays a protective role in the postnatal C57BL6 mouse testis following lactational exposure to the neonatal goitrogen, propylthiouracil (PTU). To elucidate the transcriptional profile mediating this phenotypic effect, we monitored changes in testicular gene expression at postnatal days (PNDs) 15 and 25 in Akt1+/+, Akt1+/-, and Akt1-/- testes following exposure to 0.01% PTU allowing us to determine changes in gene expression due to 1.) genotype effects; 2.) exposure effects; and 3.) genotype-by-exposure interactions. Early PTU-dependent gene changes included genes involved in lipid metabolism, spermatid differentiation, meiosis and adhesion. Early Akt1-dependent effects were associated with germ cell development, spermatid development and differentiation, and sperm motility. By PND25, the Akt1 gene-environment interaction had pronounced effects on genes associated with Sertoli cell (SC) differentiation and claudin-associated junctional formation suggesting delayed formation of the blood-testis barrier (BTB). To confirm these observations, biotin tracer experiments demonstrated a permeable blood-testis barrier in PTU-exposed PKB/Akt1-/- tubules as late as PND25 compared to PTU-exposed Akt1+/+ seminiferous tubules. Transmission electron microscopy demonstrated altered SC morphology, aberrant SC localization, and disorganized actin bundle formation. Taken together, loss of Akt1 coupled with postnatal exposure to the neonatal goitrogen, PTU, in the testis contributes to a transcriptional profile associated with impaired integrity of the blood-testis barrier. In summary, the Akt1-/- mouse represents a potentially important model to study BTB formation and reassembly in response to male reproductive toxicants and the various signaling networks which mediate these responses. The microarray analysis employed a balanced factorial design, with one chip created for each of three mice under each experimental condition: mouse genotype (Akt1+/+, Akt1+/-, and Akt1-/-), exposure (PTU and Control), and age (sacrificed at PND15 and 25), with a total of 36 mice and 36 chips. MoGene 1.0 st v1 arrays were used for the samples from PND 15 and Mouse Genome 430 2.0 arrays were used for the samples from PND 25. One chip, PTU-exposed, Akt1-/-, PND25, was determined to not be of high quality and was not included in the analysis or provided here.
2011-09-03 | E-GEOD-28664 | biostudies-arrayexpress
Project description:Thyroid hormones (THs) influence testis development, with early life hypothyroidism resulting in smaller testes in neonates. Developmental exposure to thyroperoxidase (TPO)-inhibiting drugs such as propylthiouracil (PTU) and methimazole (MMI) also impair testis development in rodents by reducing TH levels, leading to smaller testes due to for instance disrupted Sertoli cell proliferation and maturation. Comparable effects are seen for exposure to the TPO-inhibiting pesticide amitrole, one of many environmental chemicals with TH-disrupting properties. Despite this described phenotype, the molecular underpinnings of hypothyroid-induced testis effects are less clear, complicating mechanics-based chemical toxicity testing relying on alternative test methods and omics approaches.
2026-01-07 | GSE315532 | GEO
Project description:Reproductive capacity can be altered by challenges experienced during critical periods of development, including fetal development and early neonatal life. Gossypol is a polyphenolic compound, commonly found in seeds of cotton plants, that impairs male reproduction. In this study, we investigated whether the exposure to gossypol in utero and during lactation alters testis development and testis gene expression in sheep.
2019-07-04 | GSE133811 | GEO
Project description:The blood-brain barrier (BBB) plays a vital role in regulating the passage of biomolecules between the bloodstream and the central nervous system (CNS) while also protecting the CNS from pathogens. Pericytes reside at the interface between the endothelial cells that form the vessel walls and the brain parenchyma. These cells are critical for maintaining BBB integrity and regulate vessel permeability, blood flow, and immune cell migration. In this study, we developed a novel serum-free protocol to generate neural crest cell-derived pericytes (NCC-PCs) from human pluripotent stem cells (hPSCs). These NCC-PCs enhance BMEC barrier function and can be co-cultured with hPSC-derived brain microvascular endothelial cells (BMECs) in a co-culture BBB model that recapitulates the in vivo cellular interactions at the BBB. We used this model to evaluate the pathological consequences of BBB exposure to highly neuroinvasive flaviviruses. Our results identify a previously undescribed role for NCC-PCs in maintaining BMEC barrier integrity during infection and reducing the spread of viral infection to the CNS.
2025-12-08 | GSE302439 | GEO
Project description:Here, we aimed to apply a TMT based quantitative phosphoproteomics approach to investigate rodent thyroid toxicity. For this purpose, male Wistar rats have been exposed to a direct (6-propyl-2-thiouracil, PTU) and an indirect (phenytoin) thyroid toxicant, respectively. Thereby, two doses (low:5ppm for PTU and 300ppm for phenytoin , high: 50ppm for PTU and 2400ppm for phenytoin) and three exposure time phase (short: 2 weeks, long:4 weeks, and long+recovery: 4weeks+2weeks) were investigated, allowing insights into the modes of action during thyroid toxicity. Phosphoproteomics were applied to liver.
2024-10-25 | PXD030254 | Pride
Project description:We investigated if a serum microRNA signatured correlated with the presence of thyroid-mediated developmental neurotoxicity in the rat. We isolated serum from control (euthyroid) and exposed (hypothyroid) rat pups on PN8. The maternal exposure utilized to induce developmental hypothyroidism was propylthiouracil (PTU). PTU was administered in the drinking water during pregnancy and lactation.
2024-09-03 | GSE240066 | GEO
Project description:An excess in thyroid hormone during rodent neonatal life causes abnormal prolifration and maturation of testicular cells, leading to reduced testis size and impairments in steroidogenesis, Sertoli cell function, spermatogenesis and fertility. The high expression of type 3 deiodinase in the neonatal testis protects this tissue from premature exposure to thyroid hormones, since this gene (Dio3) function is to degrade thyroid hormones. DIO3-deficient mice (Dio3KO) exhibit a marked reduction in Sertoli cell proliferation and testis size, abnormalities in the reproductive axis and impaired fertility (Martinez et al. 2016, Endocrinology157:1276). To identify genes that are untimely regulated by thyroid hormone in the developing testes, we have performed RNAseq in testis total RNA from wild type and DIO3KO mouse neonates.
2019-08-01 | GSE117157 | GEO
Project description:<p>Bisphenol F (BPF), a widespread environmental contaminant and a major substitute for the restricted bisphenol A (BPA), has raised increasing concerns regarding its potential male reproductive health risks, yet its underlying mechanisms remain poorly understood. This study investigates the mechanisms underlying BPF-induced testicular damage, focusing on the interplay among gut microbiota (GM) dysbiosis, histidine metabolism disruption, and ferroptosis. Using a mouse model exposed to BPF (50, 100, and 200 mg/kg/day) for 28 days, we observed significant testicular pathology, including seminiferous tubule atrophy, vacuolation, and blood-testis barrier (BTB) impairment. Metagenomic and metabolomic analyses revealed GM dysbiosis and suppressed intestinal histidine metabolism, accompanied by decreased abundance of beneficial taxa (e.g., Bacteroides, Ligilactobacillus) and increased potential pathobionts (e.g., Akkermansia, Mucispirillum). BPF exposure also inhibited the expression of the histidine transporter LAT1, reducing histidine uptake in testes. Crucially, BPF triggered testicular ferroptosis, characterized by mitochondrial damage, iron accumulation, lipid peroxidation, and downregulation of the ferroptosis regulatory system xCT-GSH-GPX4 axis. In vitro experiments using mouse Sertoli cells (mSCs) confirmed BPF-induced ferroptosis, which was mitigated by the exogenous histidine supplementation. Histidine administration in vivo ameliorated testicular damage, restored BTB integrity, and reversed ferroptotic markers. Our findings unveil a novel “GM-histidine-testis” axis as a key mechanistic pathway for BPF-induced reproductive toxicity, providing critical insights into the health risks of emerging environmental pollutants and suggesting potential dietary intervention strategies.</p>
2026-05-26 | MTBLS13997 | MetaboLights