Regulation of sperm motility by cell-signalling events in human sperm

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Achikanu, Cosmas Ezekaibeya (2017). Regulation of sperm motility by cell-signalling events in human sperm. University of Birmingham. Ph.D.

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Abstract

Ca\(^{2+}\) signals from activated Ca\(^{2+}\) channels (CatSper) and mobilisation of Ca\(^{2+}\) stores regulate human sperm cell behaviour as they ascend the female tract. I investigated the effects on human sperm [Ca\(^{2+}\)]i and behaviour of CatSper channel activation (alkaline pH and progesterone) and Ca2+-store mobilisation (4-aminopyridine, thimerosal) using a fluorescence plate reader and CASA. Extracellular alkalinisation raised pH¬i (pHi = 6.9 and 7.2 at pHo7.4 and 8.5 respectively), caused tonic elevation of [Ca\(^{2+}\)]i, which was partially inhibited by CatSper block and increased the proportion of hyperactivated cells (from 1.8±0.5 to 10.5±1.6%; n=34, P=1x10\(^{-7}\)). Progesterone elevated [Ca\(^{2+}\)]i but caused negligible hyperactivation. Co-application of these stimuli revealed little, if any, synergistic interaction. Ca\(^{2+}\)-store mobilisation (4-aminopyridine) caused prolonged [Ca\(^{2+}\)]i elevation and was associated with strong hyperactivation. Analysis of [Ca\(^{2+}\)]i and hyperactivation data from 24 different conditions in this study showed a continuous relationship between [Ca\(^{2+}\)]i and hyperactivation. The strong hyperactivating effect of store mobilisation (compared to CatSper activation) may reflect opening of store-operated channels. Human sperm behaviour assessed over a 180 s recording revealed regular ‘switching’ between progressive and various hyperactivated types. Mobilisation of Ca\(^{2+}\) stores potently increased hyperactivated behaviour and suppressed the rate of behavioural switching.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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