title: Distinct purinergic signaling pathways in prepubescent mouse spermatogonia.
abstract: Spermatogenesis ranks among the most complex, yet least understood, developmental processes. The physiological principles that control male germ cell development in mammals are notoriously difficult to unravel, given the intricate anatomy and complex endo- and paracrinology of the testis. Accordingly, we lack a conceptual understanding of the basic signaling mechanisms within the testis, which control the seminiferous epithelial cycle and thus govern spermatogenesis. Here, we address paracrine signal transduction in undifferentiated male germ cells from an electrophysiological perspective. We identify distinct purinergic signaling pathways in prepubescent mouse spermatogonia, both in vitro and in situ. ATP-a dynamic, widespread, and evolutionary conserved mediator of cell to cell communication in various developmental contexts-activates at least two different spermatogonial purinoceptor isoforms. Both receptors operate within nonoverlapping stimulus concentration ranges, display distinct response kinetics and, in the juvenile seminiferous cord, are uniquely expressed in spermatogonia. We further find that spermatogonia express Ca(2+)-activated large-conductance K(+) channels that appear to function as a safeguard against prolonged ATP-dependent depolarization. Quantitative purine measurements additionally suggest testicular ATP-induced ATP release, a mechanism that could increase the paracrine radius of initially localized signaling events. Moreover, we establish a novel seminiferous tubule slice preparation that allows targeted electrophysiological recordings from identified testicular cell types in an intact epithelial environment. This unique approach not only confirms our in vitro findings, but also supports the notion of purinergic signaling during the early stages of spermatogenesis.
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: David
authors: 0000-0002-6692-2388
authors: D
authors: Fleck
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: Nadine
authors: N
authors: Mundt
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: Felicitas
authors: F
authors: Bruentgens
authors: Institute of Bio- and Geosciences (IBG), IBG-1: Biotechnology, Research Center Jülich, D-52425 Jülich, Germany.
authors: Petra
authors: P
authors: Geilenkirchen
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: Patricia A
authors: PA
authors: Machado
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: Thomas
authors: T
authors: Veitinger
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: Sophie
authors: S
authors: Veitinger
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: Susanne M
authors: SM
authors: Lipartowski
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: Corinna H
authors: CH
authors: Engelhardt
authors: Institute of Bio- and Geosciences (IBG), IBG-1: Biotechnology, Research Center Jülich, D-52425 Jülich, Germany.
authors: Marco
authors: M
authors: Oldiges
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany.
authors: Jennifer
authors: J
authors: Spehr
authors: Department of Chemosensation, Institute for Biology II, RWTH Aachen University, D-52074 Aachen, Germany m.spehr@sensorik.rwth-aachen.de.
authors: Marc
authors: 0000-0001-6616-4196
authors: M
authors: Spehr
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D058905:Purinergic Agents / Q000378:metabolism*; D012671:Seminiferous Tubules / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology; D013093:Spermatogonia / Q000378:metabolism* / Q000502:physiology*
chemical_list: D024681:Potassium Channels, Calcium-Activated; D058905:Purinergic Agents; D000255:Adenosine Triphosphate