Sex Differences in Urinary Extracellular Vesicles Originating from the Genitourinary System in Health and Disease

Area of Science:

• Biomarker Discovery
• Urology
• Reproductive Medicine
• Extracellular Vesicle Biology

Background:

• Urinary extracellular vesicles (uEVs) are promising non-invasive biomarkers for urogenital and reproductive system diseases.
• uEVs contain molecular cargo reflecting tissue origin, with potential sex-specific differences due to diverse organ sources and physiological factors.
• Current research on uEVs for renal and urological diseases is biased towards male cohorts, creating a knowledge gap in sex-specific biomarker applications.

Purpose of the Study:

• To review and compare existing literature on male versus female urinary extracellular vesicles (uEVs).
• To identify sex-specific differences in uEV composition and function.
• To provide insights for improving rigor and reproducibility in uEV studies for inclusive health research.

Main Methods:

• Comprehensive literature review of studies comparing male and female urinary extracellular vesicles (uEVs).
• Analysis of orthogonal methods used across different studies to characterize uEVs.
• Synthesis of current knowledge on sex-based variations in uEV biomolecular cargo and function.

Main Results:

• Significant knowledge gaps exist regarding sex-specific differences in urinary extracellular vesicle (uEV) composition and function.
• Sampling bias in current studies, predominantly using male cohorts, hinders understanding of uEVs in women's health.
• Variability in uEV studies may stem from diverse methodologies and biological factors influencing sex differences.

Conclusions:

• Addressing the knowledge gap in sex-specific urinary extracellular vesicle (uEV) differences is critical for equitable diagnostic and therapeutic advancements.
• Standardizing methodologies and increasing cohort diversity are essential for reproducible and translational uEV research.
• Future research must focus on understanding and leveraging sex-specific uEV profiles for personalized medicine in both men's and women's health.