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Androgen receptor-mediated apoptosis in bovine testicular induced pluripotent stem cells in response to phthalate esters
- Source :
- Cell Death & Disease
- Publication Year :
- 2013
- Publisher :
- Springer Science and Business Media LLC, 2013.
-
Abstract
- The androgen receptor (AR) has a critical role in promoting androgen-dependent and -independent apoptosis in testicular cells. However, the molecular mechanisms that underlie the ligand-independent apoptosis, including the activity of AR in testicular stem cells, are not completely understood. In the present study, we generated induced pluripotent stem cells (iPSCs) from bovine testicular cells by electroporation of octamer-binding transcription factor 4 (OCT4). The cells were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4, which maintained and stabilized the expression of stemness genes and pluripotency. The iPSCs were used to assess the apoptosis activity following exposure to phthalate esters, including di (2-ethyhexyl) phthalates, di (n-butyl) phthalate, and butyl benzyl phthalate. Phthalate esters significantly reduced the expression of AR in iPSCs and induced a higher ratio of BAX/BCL-2, thereby favoring apoptosis. Phthalate esters also increased the expression of cyclin-dependent kinase inhibitor 1 (p21Cip1) in a p53-dependent manner and enhanced the transcriptional activity of p53. The forced expression of AR and knockdown of p21Cip1 led to the rescue of the phthalate-mediated apoptosis. Overall, this study suggests that testicular iPSCs are a useful system for screening the toxicity of environmental disruptors and examining their effect on the maintenance of stemness and pluripotency, as well as for identifying the iPSC signaling pathway(s) that are deregulated by these chemicals.
- Subjects :
- p53
Male
Cancer Research
medicine.medical_specialty
Induced Pluripotent Stem Cells
Immunology
Phthalic Acids
Apoptosis
Biology
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Internal medicine
Testis
nuclear reprogramming
medicine
Animals
Induced pluripotent stem cell
Gene knockdown
testis cells
Phthalate
Cell Biology
Cellular Reprogramming
toxicity screening
Cell biology
Androgen receptor
Endocrinology
chemistry
environmental hormone
Receptors, Androgen
Original Article
Cattle
Tumor Suppressor Protein p53
Stem cell
Signal transduction
Leukemia inhibitory factor
Signal Transduction
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....6df2894996444295602c9ba00602c23e