• Bourgeonal and Its Role in Human Sperm Chemotaxis
  • Arefeh Gholamhosseini,1,*
    1. M.sc Student of Anatomical Sciences ,Lorestan University of Medical Sciences


  • Introduction: Bourgeonal is an aromatic aldehyde with the chemical formula C₁₁H₁₂O and is recognized as a specific agonist of the human olfactory receptor OR1D2, which is expressed on the surface of human sperm cells. This receptor belongs to the family of G protein-coupled receptors (GPCRs), a large and diverse group of membrane proteins responsible for transmitting extracellular signals into intracellular responses. OR1D2 plays a pivotal role in sperm chemotaxis, the directed movement of sperm towards chemical cues released by the female reproductive tract, facilitating sperm navigation to the oocyte for successful fertilization.
  • Methods: Upon binding to OR1D2, Bourgeonal activates intracellular cyclic adenosine monophosphate (cAMP)-dependent signaling pathways. This activation leads to the opening of voltage-sensitive ion channels, notably the CatSper channel (cation channel of sperm), which is essential for calcium ion influx into the sperm cytoplasm. The resulting increase in intracellular calcium concentration enhances sperm motility by promoting hyperactivation—a vigorous and asymmetric flagellar beating pattern—and guides spermatozoa towards the source of the chemical signal, thereby increasing the likelihood of encountering the oocyte. Functional studies employing fluorescence calcium imaging and fluorimetric assays have demonstrated that Bourgeonal induces dose-dependent calcium influx in human spermatozoa. The specificity of this response is confirmed by the inhibition of calcium signals upon application of OR1D2 antagonists, adenylate cyclase inhibitors, and CatSper blockers. These findings highlight the direct role of OR1D2 and associated intracellular pathways in mediating sperm chemotactic responses. Moreover, advanced microfluidic assays simulating the in vivo microenvironment have shown that spermatozoa actively aggregate and orient themselves along the concentration gradient of Bourgeonal, demonstrating its potent chemoattractant properties.
  • Results: At the molecular level, activation of OR1D2 engages the olfactory G protein alpha subunit (Gα\_olf), which stimulates adenylate cyclase type III, resulting in increased intracellular cAMP production. This second messenger triggers downstream effectors, potentially including protein kinase A (PKA), which modulate cytoskeletal dynamics and flagellar motility. However, emerging evidence suggests that cAMP may also activate the CatSper channel through PKA-independent pathways, implicating a complex regulatory mechanism requiring further biochemical elucidation. Beyond its role as a chemotactic agent, Bourgeonal serves as an invaluable research tool in reproductive biology. It provides a controllable and reproducible stimulus to investigate the olfactory sensory mechanisms of human sperm, particularly the function of OR1D2 and CatSper channels. In assisted reproductive technologies (ART), such as in vitro fertilization (IVF), Bourgeonal has been proposed as a functional marker to select sperm with optimal chemotactic responsiveness and motility, potentially improving fertilization rates and clinical outcomes. Conversely, diminished or absent sperm responses to Bourgeonal may indicate defects in sperm signaling pathways and serve as a biomarker for male infertility. Although Bourgeonal itself is not naturally present in the female reproductive tract, its structural similarity to endogenous ligands in female genital secretions—especially during the peri-ovulatory phase—supports the hypothesis that natural chemoattractants exist which guide sperm in vivo. Identifying these endogenous molecules and deciphering their interaction with OR1D2 remains a key objective for understanding sperm selection and fertilization processes. Furthermore, the physiological relevance of Bourgeonal analogs extends to their potential impact on sperm capacitation, acrosome reaction, and fertilization competence.
  • Conclusion: Recent studies have also explored the potential immunomodulatory effects of Bourgeonal-induced signaling, suggesting that chemotactic stimuli might influence sperm interaction with the female immune environment. Understanding such crosstalk could shed light on mechanisms of immune tolerance necessary for successful fertilization and early embryo development. conclusion Bourgeonal represents a powerful and versatile molecular probe in the study of human sperm chemotaxis and signal transduction. Through activation of the OR1D2 receptor and the CatSper calcium channel, Bourgeonal orchestrates sperm motility and directional movement crucial for fertilization. Continued research into the molecular regulation of this pathway may pave the way for novel diagnostic tools and therapeutic strategies targeting male infertility, as well as optimized protocols in assisted reproduction. Advances in this field hold promise for enhancing reproductive outcomes and deepening our understanding of human fertilization biology.
  • Keywords: Bourgeonal Human sperm chemotaxis Male infertility Olfactory signalin ART