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Updated: Aug 22, 2025

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Short-Chain Fatty Acids Modulate Sperm Migration through Olfactory Receptor 51E2 Activity
Emanuela Teveroni1, Fiorella Di Nicuolo1, Edoardo Vergani2
1International Scientific Institute "Paul VI", ISI, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
International Journal of Molecular Sciences
|November 11, 2022
Summary
Olfactory receptor 51E2 (OR51E2) on sperm binds short-chain fatty acids (SCFAs), enhancing sperm migration and activation. This discovery offers new avenues for treating infertility by understanding sperm-oocyte communication.
Area of Science:
- Reproductive Biology
- Chemosensation
- Sperm Physiology
Background:
- Olfactory receptors (ORs) are expressed in the male reproductive system, including spermatozoa.
- OR51E2 is found on sperm and binds short-chain fatty acids (SCFAs), suggesting a role in sperm function.
- SCFAs may be crucial for sperm chemotaxis and chemical communication between sperm and egg.
Purpose of the Study:
- To investigate the role of OR51E2 and SCFAs in sperm activation and migration.
- To demonstrate the functional interaction between OR51E2 and SCFAs in human sperm.
- To explore the potential of SCFAs in cervical mucus to influence sperm behavior.
Main Methods:
- Western blot and confocal microscopy to confirm OR51E2 expression and localization.
- Calcium-release assays to measure sperm activation upon SCFA stimulation.
- Modified swim-up assays coupled with computer-assisted sperm analysis (CASA) to evaluate sperm migration and kinematics.
- Mass spectrometry to identify SCFAs in cervico-vaginal mucus.
Main Results:
- OR51E2 activation by SCFAs leads to sperm cell activation.
- SCFAs promote directed sperm migration, improving linear orientation.
- SCFAs are present in cervical mucus and can directly activate sperm upon incubation.
- Confirmed functional link between OR51E2, SCFAs, and sperm motility/chemotaxis.
Conclusions:
- OR51E2/SCFA signaling is a key mechanism in sperm function, impacting migration and activation.
- SCFAs in the female reproductive tract may play a significant role in fertilization.
- This research provides a basis for novel fertility treatments targeting chemosensory pathways.
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