Highlights
- •SIRT1 is localized in the connecting piece of human spermatozoa.
- •Lysine acetylation is mainly found along the tail of human spermatozoa.
- •SIRT1 activation increases tyrosine phosphorylation.
- •SIRT1 activation improves human sperm responsiveness to Ca2+ ionophore challenge.
Abstract
Research question
Does sirtuin-1 (SIRT1) have a role in the human spermatozoa capacitation process?
Design
Human spermatozoa were incubated for 6 h in a capacitating medium in presence or absence
of the specific SIRT1 activator, YK 3-237. Several sperm parameters were determined
by flow cytometry: viability, acrosome reaction and mitochondria membrane status.
Sperm motility was determined objectively by computer-assisted semen analysis. Sperm
capacitation status was evaluated by the extent of protein tyrosine phosphorylation
and by the percentage of spermatozoa with the acrosome reacted by a calcium ionophore
challenge.
Results
SIRT1 was detected in the connecting piece of human spermatozoa where a lysine acetylation
pattern was mainly found along the sperm tail. SIRT1 activation accelerates the occurrence
of a phenotype associated with human sperm capacitation, with no differences seen
in the lysine acetylation pattern. After 1 h of co-incubation of YK 3-237 with human
spermatozoa, tyrosine phosphorylation levels were comparable to control levels after
6 h of incubation in capacitating conditions. In addition, the activator improved
sperm responsiveness to a Ca2+ ionophore (A23187) challenge determined by an increase in acrosome-reacted spermatozoa
(P = 0.025). Importantly, sperm viability and mitochondrial activity-related parameters
assessed by flow cytometry were not affected by YK 3-237.
Conclusion
YK 3-237 induces capacitation-related events in human spermatozoa such an increase
of tyrosine phosphorylation levels and acrosome-reacted spermatozoa after the ionophore
challenge. Together, these results show that YK 3-237 affects human spermatozoa capacitation-related
events by a mechanism independent of protein lysine acetylation but dependent on bicarbonate
and calcium.
Keywords
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Biography
David Martín-Hidalgo is a biology reproductive researcher with a veterinary background. He is interested in improving the outcome of assisted reproductive technology in mammals, mainly humans and domestic animals. His research and expertise have been focused on the study of sperm metabolism and intracellular pathways as a tool to overcome male infertility.
Key message
This is the first study to show the role of sirtuins in the human sperm capacitation pathway. Human spermatozoa SIRT1 activated by YK 3-237 enhances capacitation-related events by bringing forward and increasing the levels of protein tyrosine phosphorylation and increasing the percentage of spermatozoa acrosome reacted after calcium ionophore challenge.
Article info
Publication history
Published online: July 18, 2022
Accepted:
July 14,
2022
Received in revised form:
July 7,
2022
Received:
March 21,
2022
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
