Molecular Reproductive Physiology

 

Sensory Signal Transduction in Sperm

The detection of chemical and physical cues, which provides information on food, mates, danger, and pathogens, is essential for the survival of whole animals as well as for single cells. Sperm are a powerful model to elucidate the basic principles underlying sensory signal transduction. During their journey from the testis to the oviduct, mammalian sperm are exposed to different chemical milieus and physical and chemical cues guide sperm to the egg. In mammals, sperm must cover distances of several centimeters to reach the egg. Swimming up the oviduct resembles a relay race during which sperm might be instructed by long- and short-range cues to navigate by chemotaxis, rheotaxis, thermotaxis, or a combination thereof. The signaling pathways and molecules that govern sensory signaling in sperm are similar to those in sensory neurons that detect for example mechanical force, odors, or light. By the kinetic stopped- and quenched-flow technique and patch-clamp recordings, combined with fluorescent ion- and voltage-sensitive indicators, we study sensory signal transduction in human, mouse, and sea urchin sperm. In particular, we are interested in the ion channels, receptors, and cellular messengers that allow sperm to register chemical cues released by the egg as well as oviductal flow velocities and temperature gradients. We are investigating the physiology of CatSper Ca2+ channels, sNHE Na+/H+ exchangers, Slo3 K+ channels, Hv1 voltage-gated H+ channels, and the plasma membrane Ca2+-ATPase PMCA4. Moreover, by high-speed microscopy, we study the control of the swimming behavior by chemical cues and gradients of flow velocities.

 

Mechanisms underlying Male Infertility

Infertile men may suffer from insufficient sperm production, abnormal sperm morphology, severely impaired or absent sperm motility, or combinations thereof. Such obvious phenotypes are identified by classical semen analysis. However, in about 15% of the patients, the infertility is rather due to a dysfunction of the sperm, i.e. semen analysis yields parameters within normal limits. The mechanisms underlying human sperm dysfunction have remained enigmatic, not least, because the transfer of knowledge on molecular and cellular sperm physiology into the clinic has been neglected. We suspect that a defective function of sperm-specific ion channels, i.e CatSper and Slo3, underlies many cases of, as yet, unexplained sperm dysfunction.Therefore, by a function-to-gene approach, we study the role of CatSper and Slo3 in sperm from patients seeking for assisted reproduction. Thereby, we aim to shed light on the mechanisms underlying sperm dysfunction and male infertility, facilitate evidence-based selection of Assisted Reproductive Technology (ART) treatment.