ArticleToxicological sciences : an official journal of the Society of Toxicology2008
Cadmium-induced activation of stress signaling pathways, disruption of ubiquitin-dependent protein degradation and apoptosis in primary rat Sertoli cell-gonocyte cocultures.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 92 citations in OpenAlex.
- Environmental estrogens and animal reproductive health: mechanisms, biomarkers, and intervention approaches.Journal of animal science and biotechnology · 2026Review
- Impact of Cadmium Toxicity on Testicular Function: Risk of Male Infertility.Life (Basel, Switzerland) · 2026Review
- Cadmium-induced DAG-PKC/IP3-Ca2+ double signaling pathway and cell injury in gill of freshwater crabs Sinopotamon henanense.PloS one · 2026Article
- Cadmium-Induced Mitochondrial and MAMs Dysregulation in Rat Testis: The Protective Role of D-Aspartate.Environmental toxicology · 2026Article
- Cd stabilizes HIF-1α under normoxic conditions via lysine-63-linked ubiquitination and induces ER stress and cell proliferation.Toxicological research · 2025Article
- Revisiting cadmium-induced toxicity in the male reproductive system: an update.Archives of toxicology · 2024Review
- The Role of Chlorella vulgaris in Attenuating Infertility Induced by Cadmium Chloride via Suppressing Oxidative Stress and Modulating Spermatogenesis and Steroidogenesis in Male Rats.Biological trace element research · 2024Article
- Cadmium-induced impairment of spermatozoa development by reducing exosomal-MVBs secretion: a novel pathway.Aging · 2023Article
- Defective Mitochondrial Dynamics and Protein Degradation Pathways Underlie Cadmium-Induced Neurotoxicity and Cell Death in Huntington's Disease Striatal Cells.International journal of molecular sciences · 2023Article
- Zinc restores functionality in porcine prepubertal Sertoli cells exposed to subtoxic cadmium concentrationFrontiers in endocrinology · 2023Article
- Review
- Transcriptome sequencing reveals genes involved in cadmium-triggered oxidative stress in the chicken heart.Poultry science · 2021Article
- In-vitro spermatogenesis through testis modelling: Toward the generation of testicular organoids.Andrology · 2020Review
- Dietary cadmium chloride impairs shell biomineralization by disrupting the metabolism of the eggshell gland in laying hens.Journal of animal science · 2020Article
- Toxicological Effects of Cadmium on Mammalian Testis.Frontiers in genetics · 2020Review
- Evaluating biological activity of compounds by transcription factor activity profiling.Science advances · 2018Article
- Arsenic-induced apoptosis in the p53-proficient and p53-deficient cells through differential modulation of NFkB pathway.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2018Article
- High-mobility group box 1 regulates cytoprotective autophagy in a mouse spermatocyte cell line (GC-2spd) exposed to cadmium.Irish journal of medical science · 2017Article
- From the Cover: An Animal-Free In Vitro Three-Dimensional Testicular Cell Coculture Model for Evaluating Male Reproductive Toxicants.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- The presence of macrophages and inflammatory responses in an in vitro testicular co-culture model of male reproductive development enhance relevance to in vivo conditions.Toxicology in vitro : an international journal published in association with BIBRA · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Cadmium (Cd) is a ubiquitous environmental pollutant that has been associated with male reproductive toxicity in both humans and animal models. The underlying mechanism of this response, however, is still uncharacterized. To address this issue, we employed a recently developed and optimized three-dimensional primary Sertoli cell-gonocyte coculture system and examined the time- and dose-dependent effects of Cd on morphological alterations, cell viability, activation of stress signaling pathway proteins, and the disruption of the ubiquitin proteasome system (UPS). Our results demonstrated that Cd exposure lead to time- and dose-dependent morphological changes that are associated with the induction of apoptosis. In response to Cd, we also saw a disruption of the UPS as evaluated through the accumulation of high-molecular weight polyubiquitinated proteins (HMW-polyUb) as well as alterations in proteasome activity. Robust activation of cellular stress response, measured through the increased phosphorylation of stress-activated protein kinase/c-jun N-terminal kinase and p38, paralleled the accumulation of HMW-polyUb. In addition, p53, a key regulatory protein, was upregulated and underwent increased ubiquitination in response to Cd. To further characterize the role of the UPS in Cd cellular response, we compared the above changes with two classic proteasomal inhibitors, lactacystin, and MG132. The stress response and the accumulation of HWM-polyUb induced by Cd were consistent with the response seen with MG132 but not with lactacystin. In addition, Cd treatment resulted in a dose- and time-dependent effect on proteasome activity, but the overall Cd-induced proteasomal inhibition was unique as compared to MG132 and lactacystin. Taken together, our studies further characterize Cd-induced in vitro testicular toxicity and highlight the potential role of the UPS in this response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.