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Berberine inhibits experimental varicocele-induced cell cycle arrest via regulating cyclin D1, cdk4 and p21 proteins

M Amin1, M Razi1, F Sarrafzadeh-Rezaei2

  • 1Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Andrologia
|February 15, 2018
PubMed

Insights

Berberine (BBR) protects against experimental varicocele (VCL) by preserving testicular cell cycle machinery. This antioxidant improves germ cell health and reduces DNA fragmentation, suggesting BBR as a potential therapeutic agent for VCL-induced infertility.

Area of Science:

  • Reproductive Biology
  • Pharmacology
  • Cell Biology

Background:

  • Experimental varicocele (VCL) induces adverse effects on testicular cell cycle machinery during germ cell mitosis.
  • Oxidative stress and DNA damage are implicated in VCL-induced testicular dysfunction.
  • Berberine (BBR), a known antioxidant, has potential protective properties against cellular damage.

Purpose of the Study:

  • To investigate the protective effect of berberine (BBR) against experimental varicocele (VCL)-induced damage to cell cycle machinery in early germ cells.
  • To evaluate BBR's impact on histological alterations, cell cycle protein expression, and DNA fragmentation in a rat model of VCL.

Main Methods:

  • Thirty mature male Wistar rats were divided into control-sham, non-treated VCL, and VCL groups treated with 50 mg/kg or 100 mg/kg BBR for 60 days.
  • Histological analysis using hematoxylin and eosin (H&E) staining.
  • Immunohistochemical (IHC) staining to assess expressions of cyclin-D1, cyclin-dependent kinase-4 (cdk4), and p21.
  • DNA ladder test to evaluate testicular DNA fragmentation.

Main Results:

  • BBR administration significantly reduced the percentage of seminiferous tubules with deformed shapes, depleted germ cells, and germ cell dissociation compared to the VCL-only group.
  • IHC analysis revealed that BBR significantly reduced VCL-induced p21 expression and upregulated cyclin-D1 and cdk4 expressions (p < .05).
  • BBR treatment decreased VCL-induced testicular DNA fragmentation.

Conclusions:

  • Berberine (BBR) promotes the cell cycle by protecting cellular DNA content, down-regulating p21 expression, and maintaining cyclin-D1 and cdk4 expressions.
  • BBR demonstrates potential as a novel protective biochemical agent against experimental varicocele (VCL)-induced testicular derangements.
  • Further research is warranted to fully elucidate BBR's effects on the cell cycle process and germ cell development.
Keywords:
DNA damagecell cycleratspermatogenesisvaricocele

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