Lovastatin promotes the self-renewal of murine and primate spermatogonial stem cells

Area of Science:

• Reproductive Biology
• Stem Cell Biology
• Pharmacology

Background:

• The spermatogonial stem cell (SSC) niche is vital for maintaining sperm production and is susceptible to damage from reproductive hazards.
• Impaired SSC niches can lead to abnormal self-renewal and male infertility, with limited therapeutic options available.
• Identifying agents that can restore SSC niche function is crucial for addressing male infertility.

Purpose of the Study:

• To investigate the effects of Lovastatin on the self-renewal of mouse spermatogonial stem cells (mSSCs).
• To elucidate the underlying mechanisms by which Lovastatin influences SSCs.
• To assess Lovastatin's efficacy in promoting SSC proliferation in preclinical models of male infertility.

Main Methods:

• Screening and assessment of Lovastatin's impact on mSSC self-renewal.
• Analysis of molecular pathways, including isoprenoid intermediates, inflammation, and apoptosis.
• Evaluation of Lovastatin's effect on undifferentiated spermatogonia proliferation in busulfan-induced male gonadotoxicity models.
• Testing Lovastatin's efficacy in primate undifferentiated spermatogonia.

Main Results:

• Lovastatin significantly promotes the self-renewal of mSSCs.
• The drug inhibits inflammation and apoptosis in mSSCs by regulating isoprenoid intermediates.
• Lovastatin treatment enhanced the proliferation of undifferentiated spermatogonia in a mouse model of busulfan-induced gonadotoxicity.
• Lovastatin demonstrated efficacy in enhancing the proliferation of primate undifferentiated spermatogonia.

Conclusions:

• Lovastatin promotes the self-renewal of both murine and primate spermatogonial stem cells.
• The findings suggest Lovastatin has therapeutic potential for treating specific types of male infertility.
• Lovastatin represents a promising small compound for addressing impaired SSC niche function and restoring fertility.