WE have found that certain lectins are suitable for depleting moribund sperm which includes poor motilitiy

Henry

THanks for your replies and suggestions. My views on the subjects are as follows:

Sperm are transcriptionally silenced gametes. Yet, sperm transcripts have been widely reported and presumably, could be playing a putative role post fertilization. This paper reports that HDAC6 enzyme has a role in sperm motility, a function which is important prior to fertilization. Inhibitors of HDAC6 reduced/blocked sperm motility. Human sperm with poor motility are not inhibited by any endogenous/exogenous molecules. Therefore poor motility must have some other etiology. Historically, sperm motility has been reported to be calcium dependent. This dependence has been ascribed to sperm phosphodiesterase and dynein ATPase enzymes. The effects of calcium are dual in that low levels have been described as being conducive to forward motility whereas high levels are inhibitory giving rise to on-spot-tumbling motility. Sperm survives till about 72 hours post fertilization. During this time period, HADC6 must be very important for engendering motility. I am not aware whether HDAC6 is a calcium regulated enzyme which would make it susceptible to inhibition at high levels. It might need to be replenished for a while and the sperm HDAC6 transcripts could be important for this purpose. But this function would require an active translation mechanism in the sperm itself. However, sperm translation of transcripts has not yet been authenticated. Therefore the finding, no doubt important from the point of view of mechanism of sperm motility, is not suggestive of clinical relevance. A possibility of clinical relevance of HDAC6 sperm transcripts could emerge if experiments are undertaken to check whether these are derived from a mutated/normal gene or these are representative of a less active variant of the HADC6 gene. Alternatively, it can be hypothesized that low sperm transcript levels in sperm with poor motility vs those with normal motility could be indicative of poor testicular expression of HDAC6 gene due to defective regulatory mechanism/s, if such an experiment were to be conducted with human samples.

Thank you for your views, Dr Sharma. I have always appreciated them. We have not yet studied the expression of HDAC6 in asthenozoosperm vis a vis normal sperm, although we intend to do that. But even if we do, I do not believe that HDAC6 could be used as a biomarker for sperm motility. The hypothesis on which this study was based is that being a tubulin specific deacetylase involved in chemotactic cell movement (as has been reported by Hubbert et al., in 2002), would HDAC6 also have a role in sperm movement given that sperm axoneme is composed of microtubules  which are highly acetylated. From our observations out of this work and our work done with human sperm where we show that alpha tubulin acetylation is reduced in individuals with poor sperm motility (Bhagwat et al., Fert. Steril. 2014), we believe that HDAC6 may function as a MAP and thus be responsible for maintaining dynamic instability of the axonemal microtubules and that dynamic instability may be a pre-requisite for normal sperm motility, and we are presently testing this hypothesis.