# Exploring OR2H1-Mediated Sperm Chemotaxis: Development and Application of a Novel Microfluidic Device

## TL;DR

A new microfluidic device helps study how sperm move toward chemical signals, revealing that a compound called methional boosts sperm movement via a receptor called OR2H1.

## Contribution

A novel microfluidic device was developed and used to identify OR2H1 as a receptor mediating sperm chemotaxis via methional.

## Key findings

- Methional, a sulfur-containing aldehyde, enhances sperm migration and progressive motility.
- Methional increases intracellular calcium levels in sperm, indicating receptor activation.
- Methional improves sperm movement parameters like linearity and straightness without affecting velocity.

## Abstract

Microfluidic platforms have emerged as critical technologies for exploring sperm chemotaxis, providing precise gradient control, and facilitating in-depth behavioral assessment. We designed a novel, user-friendly microfluidic device that is optimized for human sperm morphology and motility. The device was validated using two well-established sperm chemoattractants, progesterone and bourgeonal, demonstrating its reliability and reproducibility. Given the key role of olfactory receptors (ORs) in mediating sperm chemotaxis, the newly developed device was employed to identify additional receptors that may contribute to sperm behavior. Using the Atlas database, we identified OR2H1 as a candidate receptor. It is enriched in testis-derived cells, particularly in early and late spermatids, and it is broadly expressed across human spermatozoa. We demonstrated that OR2H1’s ligand, methional, a sulfur-containing aldehyde naturally found in vaginal fluid and biosynthesized by Lactococcus lactis, significantly enhances sperm migration and progressive motility. Methional stimulation also triggered increased intracellular calcium levels, indicating receptor activation. Computer-assisted sperm analysis revealed that methional treatment improved sperm linearity, straightness, and wobble without affecting the average velocity, suggesting enhanced directional movement. These findings provide evidence that methional promotes sperm chemotaxis via OR2H1 and highlight the potential role of the vaginal microbiome in influencing human fertility.