Melatonin attenuates detrimental effects of diabetes on the niche of mouse spermatogonial stem cells by maintaining Leydig cells

Cell Death & Disease
Zhaoyu DuSha Peng

Abstract

Diabetes mellitus affects a large number of men of reproductive age and it usually leads to serious reproductive disorders. However, the underlying mechanisms and specific therapies still remain largely unknown. We observed Leydig cell loss in the testes of diabetic mice. Continuous high glycemic status of testes stimulated expression of Caspase12, Grp78, and Chop, the three ERS response factors; this might induce cell cycle arrest and apoptosis of Leydig cells in response to ERS. In these diabetic mouse models, melatonin alleviated apoptosis of testicular stromal cell induced by ERS, and promoted SSCs self-renewal by recovering Leydig cells secretion of CSF1 after 8 weeks of treatment. To explore the relationship between CSF-1 and ERS in Leydig cells, we treated Leydig tumor cell line with an activator Tuniamycin and an inhibitor 4-Phenylbutyrate of ERS. Our data showed that the CSF-1 expression in mouse Leydig cell lines decreased six-fold while reversely increasing five-fold in the 4-Phenylbutyrate-treated group. Thus, melatonin likely alleviates the loss of Leydig cells in diabetic testes and provides a healthier niche for SSCs to self-renew and continually provide healthy sperm for male fertility.

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Citations

Aug 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yike YinZhonghan Li
Jan 22, 2021·Andrologia·Gulnur KizilayYeter Topcu-Tarladacalisir
Feb 20, 2021·Stem Cells International·Mengfei ZhangJinlian Hua
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Samah A El-NewaryAbdelsamed I Elshamy
Jul 6, 2020·Acta histochemica·Érique Ricardo AlvesValéria Wanderley Teixeira
Mar 14, 2021·Tissue Engineering and Regenerative Medicine·Heba F IbrahimAmira Y Medwar
Jul 6, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Wenqing LiuJinlian Hua

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Methods Mentioned

BETA
flow cytometry
ELISA
Protein Assay

Software Mentioned

Graphpad Prism
Image J

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