Colony-stimulating factor-1 as a potential therapeutic target in asthenozoospermia

Area of Science:

• Reproductive biology
• Male infertility research
• Proteomics and molecular diagnostics

Background:

• Asthenozoospermia (AZS) is a primary cause of male infertility, characterized by reduced sperm motility.
• Seminal plasma proteins critically regulate sperm function, but AZS etiology is not fully understood.
• Colony-stimulating factor 1 (CSF-1) is implicated in sperm regulation, spermatogenesis, and maturation.

Purpose of the Study:

• To investigate the role of seminal plasma proteins, specifically CSF-1, in the pathophysiology of asthenozoospermia.
• To identify potential diagnostic biomarkers and therapeutic targets for AZS.

Main Methods:

• Proteomic analysis (DIA) of seminal plasma from healthy donors and AZS patients.
• Validation of differentially expressed proteins, focusing on CSF-1, in an independent cohort.
• In vitro functional assays using CSF-1 inhibitors (Pexidartinib) and recombinant CSF-1 to assess effects on sperm motility and mitochondrial function.

Main Results:

• Elevated seminal plasma CSF-1 levels were significantly associated with AZS.
• Pexidartinib treatment improved sperm motility in AZS patients, while recombinant CSF-1 reduced motility in healthy donors.
• CSF-1 inhibition increased intracellular ATP levels, indicating improved mitochondrial energy metabolism; CSF-1 was shown to induce mitochondrial dysfunction.

Conclusions:

• Seminal plasma CSF-1 is a potential pathogenic factor contributing to asthenozoospermia.
• CSF-1 suppresses sperm motility by impairing mitochondrial energy metabolism.
• CSF-1 serves as a promising diagnostic biomarker and therapeutic target for AZS management, with Pexidartinib as a potential treatment.