The following is a summary of the “Sirtuin 1 activator YK 3-237 stimulates capacitation-related events in human spermatozoa,” published in the Jan 2023 issue of Reproductive Biomedicine Online by Hidalgo, et al.

Capacitating medium with or without the specific sirtuin-1 (SIRT1) activator YK 3-237 was used to incubate human spermatozoa for 6 hours. Flow cytometry was used to analyze several characteristics of sperm, including their viability, acrosome reaction, and mitochondria membrane status. Computer-assisted semen analysis provided a scientifically valid method for measuring sperm motility. Protein tyrosine phosphorylation and the proportion of acrosome-reactive spermatozoa were used to assess sperm capacitation in a calcium ionophore challenge.

Human spermatozoa have been shown to have SIRT1 in their connecting piece, where lysine acetylation was found predominantly along the sperm tail. A phenotype linked to human sperm capacitation occurs more quickly following SIRT1 activation, but the pattern of lysine acetylation is unaffected. When YK 3-237 was co-incubated with human spermatozoa for 1 hour, tyrosine phosphorylation levels were similar to controls after 6 hours of incubation. In addition, as measured by an increase in acrosome-reacted spermatozoa (P = 0.025), the activator improved sperm responsiveness to a Ca2+ ionophore (A23187) challenge. 

Importantly, YK 3-237 did not affect sperm viability or parameters related to mitochondrial activity as measured by flow cytometry. However, in response to the ionophore challenge, capacitation-related events, such as elevated tyrosine phosphorylation and acrosome-reacted spermatozoa, are induced in human spermatozoa by YK 3-237. These findings demonstrate that YK 3-237 influences capacitation-related events in human spermatozoa through a mechanism that is not dependent on protein lysine acetylation but relies on bicarbonate and calcium.