Glycerophsopholipids may incorporate to biological membranes of mature human spermatozoa, enhancing & increasing their resistance to oxidative stress

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A paper, presented via abstract submission to a conference in Ururguay in 2017, by researchers exploring the role of membrane replacement therapy in the reduction of oxidative damage in spermatozoa, describes how carefully selected membrane compatible lipids improve sperm motility and potentially offers a reproductive advantage to aging or oxidatively damaged spermatozoa membranes.

The authors are: *Costa, C;* Baissazteguy, V; Santos, M; Ordoqui, R; Montes, J; Settineri, R; Nicolson, GL y Ferreira, G.

The composition of the plasma membrane is critical for the motility and viability of mature human spermatozoa. Mature spermatozoa produces reactive oxygen species that are increased during aging, producing membrane lipoperoxidation that affects their motility and viablity. Lipid reposition therapy seeks to replace damaged peroxidized lipids by a fresh mixture of glycerolphospholipids in a proportion similar to that found in most biological membranes (NTFL).

We have previously shown that the incubation of mature human spermatozoa with NTFL in the range 0.01-3%, diminishes this negative effect on motility (measured according to WHO parameters), when they are exposed to different damaging agents that increase their oxidative stress. In this report we continue the evaluation of lipid reposition therapy using mature human spermatozoa, monitoring membrane integrity as well as mitochondrial membrane potential. Our results show that NTFL 0.01-0.1% centrifuged and ultrasonicated, yields different size nanomicelles (less than 0.3 microns diameter), that can be observed at high magnification under the microscope. These nanomicelles can incorporate lipid specific fluorescent dyes that can incorporate to the biological membranes of spermatozoa after a 2hs period of incubation.

This finding suggests that NTFL also incorporates to the biological membranes when incubating spermatozoa with these fluorescent dyes.

Dose-response curves of spermatozoa motility  vs H2O2 shift their values of mean dose of inhibition towards more positive values when incubation is done in the presence of NTFL. This result indicates a protective role of NTFL against oxidative stress damage produced by H2O2. Flow cytommetry of mature human spermatozoa loaded with the dye that reports mitochondrial membrane potential, JC-1, show that incubation with NTFL increases the number of spermatozoa with more negative mitochodrial membrane potential, when they are exposed to H2O2. Studies with confocal microscopy with both mitochodrial dyes, Rhodamine 123 and JC-1 are consistent with these previous results, suhhesting an antioxidant role of NTFL that targets mitochondria. In summary, mature human spermatozoa are a good model to study lipid reposition therapy with NTFL, suggesting that LRT is effective in the prevention of damage of oxidative stress at the mitochondrial level.

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