RRC ID 30711
Author Lin YC, Kuo KK, Wuputra K, Lin SH, Ku CC, Yang YH, Wang SW, Wang SW, Wu DC, Wu CC, Chai CY, Lin CL, Lin CS, Kajitani M, Miyoshi H, Nakamura Y, Hashimoto S, Matsushima K, Jin C, Huang SK, Saito S, Yokoyama KK.
Title Bovine induced pluripotent stem cells are more resistant to apoptosis than testicular cells in response to mono-(2-ethylhexyl) phthalate.
Journal Int J Mol Sci
Abstract Although the androgen receptor (AR) has been implicated in the promotion of apoptosis in testicular cells (TSCs), the molecular pathway underlying AR-mediated apoptosis and its sensitivity to environmental hormones in TSCs and induced pluripotent stem cells (iPSCs) remain unclear. We generated the iPSCs from bovine TSCs via the electroporation of OCT4. The established iPSCs were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4 to maintain and stabilize the expression of stemness genes and their pluripotency. Apoptosis signaling was assessed after exposure to mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate. Here, we report that iPSCs were more resistant to MEHP-induced apoptosis than were original TSCs. MEHP also repressed the expression of AR and inactivated WNT signaling, and then led to the commitment of cells to apoptosis via the cyclin dependent kinase inhibitor p21CIP1. The loss of the frizzed receptor 7 and the gain of p21CIP were responsible for the stimulatory effect of MEHP on AR-mediated apoptosis. Our results suggest that testicular iPSCs can be used to study the signaling pathways involved in the response to environmental disruptors, and to assess the toxicity of environmental endocrine disruptors in terms of the maintenance of stemness and pluripotency.
Volume 15(3)
Pages 5011-31
Published 2014-3-20
DOI 10.3390/ijms15035011
PII ijms15035011
PMID 24658443
PMC PMC3975437
MeSH Animals Apoptosis / drug effects* Apoptosis / genetics Blotting, Western Cattle Cell Survival / drug effects Cell Survival / genetics Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 / genetics Cyclin-Dependent Kinase Inhibitor p21 / metabolism Diethylhexyl Phthalate / analogs & derivatives* Diethylhexyl Phthalate / pharmacology Frizzled Receptors / genetics Frizzled Receptors / metabolism Gene Expression / drug effects Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism Male Mice, SCID Pluripotent Stem Cells / cytology Pluripotent Stem Cells / metabolism RNA Interference Receptors, Androgen / genetics Receptors, Androgen / metabolism Reverse Transcriptase Polymerase Chain Reaction Testis / cytology* Testis / metabolism Wnt Signaling Pathway / drug effects Wnt Signaling Pathway / genetics
IF 4.556
Times Cited 9
DNA material pCMFlag_hsOct3/4isoform1 (RDB06598).