P8: The (patho)physiology of ion channels in human sperm

Timo Strünker, Centre of Reproductive Medicine and Andrology (CeRA) (Homepage)
Christoph Brenker, Centre of Reproductive Medicine and Andrology (CeRA) (Homepage)

Project summary

We study the function of CatSper and Slo3 in sperm from patients with a battery of biophysical techniques, including motility analysis, ion- and Vm-sensitive fluorimetry, expansion microscopy, and electrophysiological patch-clamp recordings.

Male infertility is often due to defective sperm production, morphology, motility, or combinations thereof. However, a large fraction of infertile patients is normozoospermic, indicating that the infertility rests on a dysfunction of the sperm. The underlying mechanisms are largely unknown, precluding an evidence-based treatment decision.

To fertilise the egg, human sperm fulfil several demanding tasks that are orchestrated by the sperm-specific ion channels CatSper and Slo3. There is a growing body of evidence that, as yet, unexplained sperm dysfunction involves the loss of CatSper and/or Slo3 function. In this research endeavour, by a function-to-gene approach and using novel experimental tools, we investigate CatSper and Slo3 in sperm from patients seeking assisted reproduction. Thereby, we shed light on the mechanisms underlying sperm dysfunction and male infertility, enable evidence-based treatment decisions, and gain novel insights into the physiology and pathophysiology of CatSper and Slo3 in human sperm.

Electrophysiological characterisation of membrane currents in control sperm from donors and in sperm from patients lacking the CATSPER2 gene. The CATSPER2-deficient patients were identified by our novel CatSper-Activity-Test. The deletion of CATSPER2 results in the loss of CatSper function.

 

In particular, we want to elucidate how CatSper and Slo3 interplay to control sperm function and, thereby, the fertilisation process.