iTRAQ-based proteomics analysis of diethylstilbestrol induced dysfunction of testicular gubernaculum development in mouse

Background Diethylstilbestrol (DES) has been shown to disrupt the morphology and proliferation of gubernaculum testis cells. Objective This study aimed to elucidate the mechanism underlying DES induced damage to gubernaculum testis based on proteome analysis. Results Neonatal mice were exposed to DE...

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Bibliographic Details
Published in:Molecular & cellular toxicology 2022, 18(4), , pp.557-568
Main Authors: Ping, Hongyan, Wang, Degang, Fu, Maxian, Chen, Kaihong, Zhang, Jiuhong, Li, Ke, Jiang, Xuewu, Duan, Shouxing, Zhang, Xuan
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Calcium signalling
Cardiac muscle
Cell Biology
Cell proliferation
Cryptorchidism
Cytology
Diethylstilbestrol
Gonads
Life Sciences
Muscle contraction
Neonates
Original Article
Oxidative phosphorylation
Pharmacology/Toxicology
Phosphorylation
Proteomes
Proteomics
Quantitation
Signal transduction
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Summary:Background Diethylstilbestrol (DES) has been shown to disrupt the morphology and proliferation of gubernaculum testis cells. Objective This study aimed to elucidate the mechanism underlying DES induced damage to gubernaculum testis based on proteome analysis. Results Neonatal mice were exposed to DES or control vehicle and the gonads were collected for isobaric tags for relative and absolute quantitation based proteomics analysis. We found that at the early and late stages of gubernaculum development, treatment with different concentrations of DES upregulated the expression of proteins which were generally involved in several function categories including single-organism process, cellular process, binding, catalytic activity, cell part and organelle. KEGG pathway analysis showed that cardiac muscle contraction, oxidative phosphorylation, calcium signaling and cGMP-PKG signaling pathway were the most dysregulated pathways associated with DES in the late stage of gubernaculum development, while steroid biosynthesis was the only enriched pathway in the early stage of gubernaculum development. Conclusion Proteomics profiling and functional analysis reveal new clues on how DES interferes with cellular processes and disrupts the development of gubernaculum. These findings have potential applications in the treatment of genitourinary diseases such as cryptorchidism.
ISSN:1738-642X
2092-8467
DOI:10.1007/s13273-022-00228-y