Experimental Varicocele Negatively Affects The Spermatogonial Stem Cells Self-Renewal at VI and XII Stages of Spermatogenesis by Suppressing Nanog-Related Mechanism; Cross-Link with Niche Factors and Cell Cycle Regulators

سال انتشار: 1397
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 89

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SCROYAN14_189

تاریخ نمایه سازی: 14 آبان 1403

چکیده مقاله:

Background: The spermatogonial stem cells division is partiallyregulated by cyclin D۱ and cyclin dependent kinase (CDK-۴)interaction. Moreover, the glial cell line-derived neurotrophicfactor (GDNF), plays a critical role in regulating the SSCs selfrenewal,especially at I-VI stages of spermatogenesis. In line,the interaction of GDNF with its receptors c-RET and Gfrα۱,finally ends to Cyclin D۱ and CDK-۴ interaction. The P۲۱,as CDK-inhibitor protein, negatively influences the SSCs divisionvia interacting with the cyclinD۱/CDK۴ complex and/or through suppressing the Nanog expression, as key regulatorof SSCs self-renewal at stage XII. The present study was conductedto illustrate the cross-link between cell cycle regulatorsand Sertoli cells-related niche elements as well as their interactionin unique network with SSCs proliferation in experimentalvaricocele (VCL) condition.Materials and Methods: ۱۲ mature male Wistar rats were dividedinto two groups; control-sham group (with simple laparotomy)and ۲ months VCL-induced group. The mRNA andprotein levels of Cycin D۱, CDK۴ and P۲۱ as well as stem cellmarkers (GDNF, Gfrα۱, c-Ret, Nanog) were analyzed by RTPCRand western blotting techniques, respectively. the immunohistochemistrystaining was done to analyze the protein expressionat I-VI and XII stages of seminiferous tubules. Finally,the correlations between the data of GDNF, Gfrα۱, c-Ret, CyclinD۱, CDK-۴ and p۲۱ with Nanog expression was analyzed.Results: The animals in VCL-induced group exhibited diminishedGDNF, Gfrα۱, c-RET, Nanog, Cyclin D۱ and CDK-۴, andrepresented enhanced p۲۱ expressions versus control group.The seminiferous tubules at I-VI and XII stages exhibited enhancedexpression of p۲۱+ cells, and represented a significantreduction in GDNF+, Gfrα۱+, c-RET+, Nanog+, Cyclin D۱+and CDK-۴+ and Nanog+ cell population. Finally, the statisticalanalyses revealed a positive correlation between GDNF, Gfrα۱,c-Ret and Cyclin D۱, CDK-۴ (at stages of I-VI). Moreover, theNanog expression was negatively correlated with p۲۱ expression(at stage of XII).Conclusion: The VCL pathologically affects the Nanogdependentcell proliferation via suppressing the Sertoli cellsmaintainedniche factors and suppressing the cell cycle machinery.Thereafter, suppressed Nanog expression significantlydown-regulates the SSCs self-renewal, leading to arrested apermatogenesis.

نویسندگان

S Moshari

Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

F Sarrafzadeh-Rezaie

Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

H Hassani-Bafrani

Department of Anatomy, Faculty of Medical Sciences, Kashan University, Kashan, Iran

H Rashtbari

Department of Anatomy, Faculty of Medical Sciences, Kashan University, Kashan, Iran

H Najaran

Department of Anatomy, Faculty of Medical Sciences, Kashan University, Kashan, Iran

M Amin

Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran