Myeloperoxidase inhibitor AZD5904 enhances human sperm function in vitro

Area of Science:

• Reproductive biology
• Andrology
• Pharmacology

Background:

• Male infertility affects 50% of couples trying to conceive, with oxidative stress (OS) being a significant contributing factor in infertile men.
• OS negatively impacts sperm motility, fertilization capacity, and DNA integrity, making it a therapeutic target.

Purpose of the Study:

• To investigate the effect of AZD5904, a myeloperoxidase inhibitor (MPOi), on human sperm function in an in vitro model of OS.

Main Methods:

• Human spermatozoa were incubated with activated neutrophils to induce OS, with parallel samples co-incubated with AZD5904.
• Sperm motility and functional motility (sperm penetration assay) were assessed at 2 and 24 hours.
• Computer-assisted sperm analysis was used to evaluate sperm motility.

Main Results:

• While total and progressive sperm motility showed no significant differences, AZD5904 treatment led to a significant increase (≥20%) in sperm penetration in 35.6% of samples.
• This improvement in functional motility suggests enhanced fertilization capacity in a subset of treated sperm samples.

Conclusions:

• AZD5904 demonstrated a positive effect on human sperm function in vitro, specifically in sperm penetration, indicating potential for improved fertilization.
• These preliminary findings warrant further investigation through clinical trials to validate AZD5904 as a novel therapeutic approach for male infertility.