Di Nicuolo Fiorella, Teveroni Emanuela, Devigili Alessandro, Gasparini Clelia, Urbani Andrea, Ghi Tullio, Pontecorvi Alfredo, Milardi Domenico, Mancini Francesca
International Scientific Institute Paul VI, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Department of Basic Biotechnological Sciences, Intensive and Perioperative Clinics, Catholic University of Sacred Heart, 00168 Rome, Italy.
Cells. 2025 Jun 20;14(13):944. doi: 10.3390/cells14130944.
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 , 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.
微流控平台已成为探索精子趋化性、提供精确梯度控制以及促进深入行为评估的关键技术。我们设计了一种新颖、用户友好的微流控装置，该装置针对人类精子形态和活力进行了优化。使用两种成熟的精子化学引诱剂孕酮和波旁醛对该装置进行了验证，证明了其可靠性和可重复性。鉴于嗅觉受体（ORs）在介导精子趋化性中的关键作用，新开发的装置被用于识别可能影响精子行为的其他受体。利用阿特拉斯数据库，我们确定OR2H1为候选受体。它在睾丸来源的细胞中富集，特别是在早期和晚期精子细胞中，并且在人类精子中广泛表达。我们证明，OR2H1的配体甲硫醛（一种天然存在于阴道液中并由其生物合成的含硫醛）显著增强精子迁移和渐进性运动。甲硫醛刺激还引发细胞内钙水平升高，表明受体被激活。计算机辅助精子分析显示，甲硫醛处理改善了精子的直线性、笔直度和摆动度，而不影响平均速度，表明定向运动增强。这些发现提供了证据，证明甲硫醛通过OR2H1促进精子趋化性，并突出了阴道微生物群在影响人类生育方面的潜在作用。
