Insight into the physiological architecture of seminiferous tubule Ca2+ signaling

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Despite the essential biological role of fertilization, a conceptual mechanistic understanding of the physiological principles that control the spermatogenic cycle is still lacking. Therefore, the long-term goal of my research is to gain insight into the molecular and cellular mechanisms that orchestrate the life-long mass proliferation and differentiation process of spermatogenesis. In this proposal, I focus on a critical component of most cellular signaling pathways – Ca2+ – and aim to unravel the role of this universal messenger molecule in testicular (patho)physiology. In the seminiferous epithelium, knowledge about Ca2+ signaling and its role in the spermatogenic cycle is rather fragmentary. While it has been demonstrated that endocrine control of spermatogenesis by both FSH and testosterone functionally converges on Ca2+ mobilization in Sertoli cells, the underlying mechanisms remain elusive. Built on a solid foundation of unpublished pilot research and innovative methodology, I propose an integrated multi-faceted research strategy that (i) targets spontaneous Ca2+ signals in Sertoli and germ cells, respectively, and that (ii) aims to address the dynamic profile of such signals as a function of an animal’s endocrine state. A distinctive feature of this proposal is the transfer of well-established neurobiological methodology, such as brain slice physiology and multi-photon in vivo imaging, to the field of reproductive biology. I firmly believe that adoption of this trans-disciplinary approach will provide a wealth of exciting novel information on one of the most enigmatic physiological processes – spermatogenesis.