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Unraveling the Molecular Mechanisms Underlying N-formyl-L-aspartate-mediated Sperm Chemotaxis
CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(S 01): S1-S16
DOI: DOI: 10.1055/s-0044-1788205
*Corresponding author: (e-mail: pparte@nirrh.res.in; durva gib@nirrh.res.in).
Abstract :
Background: In in vitro fertilization (IVF), many sperms are capable of fertilization, increasing the rates of polyspermy and compromising embryo development. Chemotaxis, a chemical guiding mechanism, controls sperm quality and quantity reaching the egg. N-formyl-l-aspartate (NFA), a bacterial chemotaxis metabolite and beta-2-adrenergic receptor agonist, was found to be increased in ovulatory phase oviductal fluid.
Methodology: The study explores the mechanism of chemotaxis mediated by NFA through various strategies including activation of chemotactic signaling, identification, and pharmacological inhibition of the cognate receptor, secondary messenger measurement, and effect on capacitation or acrosome reaction.
Results: NFA showed a dose–response curve typical of chemotaxis with maximum response observed at 0.01 M. β-2-ARs were localized on sperm head and mid-piece of the flagella and inhibition of sperm chemotaxis by ICI-118,551, a β-2-AR antagonist, confirms that sperms respond chemotactically to NFA via β-2-AR. At 0.01 M, NFA induced an increase in Ca2+ in sperms and this was abrogated on exposure to ICI-118,551. Furthermore, NFA did not induce capacitation or acrosome reaction. The study suggests that NFA-mediated chemotaxis involves interaction with β-2-AR on sperm flagella, activating intracellular calcium mobilization without affecting intracellular cAMP levels, facilitating linear swimming toward an egg.
Conclusion: This research suggests a molecular mechanism for understanding signal transduction pathways during sperm chemotaxis, potentially using NFA as a chemoattractant to improve IVF “take home baby” rates.
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
*Corresponding author: (e-mail: pparte@nirrh.res.in; durva gib@nirrh.res.in).
Abstract :
Background: In in vitro fertilization (IVF), many sperms are capable of fertilization, increasing the rates of polyspermy and compromising embryo development. Chemotaxis, a chemical guiding mechanism, controls sperm quality and quantity reaching the egg. N-formyl-l-aspartate (NFA), a bacterial chemotaxis metabolite and beta-2-adrenergic receptor agonist, was found to be increased in ovulatory phase oviductal fluid.
Methodology: The study explores the mechanism of chemotaxis mediated by NFA through various strategies including activation of chemotactic signaling, identification, and pharmacological inhibition of the cognate receptor, secondary messenger measurement, and effect on capacitation or acrosome reaction.
Results: NFA showed a dose–response curve typical of chemotaxis with maximum response observed at 0.01 M. β-2-ARs were localized on sperm head and mid-piece of the flagella and inhibition of sperm chemotaxis by ICI-118,551, a β-2-AR antagonist, confirms that sperms respond chemotactically to NFA via β-2-AR. At 0.01 M, NFA induced an increase in Ca2+ in sperms and this was abrogated on exposure to ICI-118,551. Furthermore, NFA did not induce capacitation or acrosome reaction. The study suggests that NFA-mediated chemotaxis involves interaction with β-2-AR on sperm flagella, activating intracellular calcium mobilization without affecting intracellular cAMP levels, facilitating linear swimming toward an egg.
Conclusion: This research suggests a molecular mechanism for understanding signal transduction pathways during sperm chemotaxis, potentially using NFA as a chemoattractant to improve IVF “take home baby” rates.
No conflict of interest has been declared by the author(s).
Publication History
Article published online:
08 July 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India