Professor Division of Germ Cell Biology, National Institute for Basic Biology Okazaki, Aichi, Japan
Abstract Authors: Shosei Yoshida1; Toshiyuki Sato1 1. Division of Germ Cell Biology, National Institute for Basic Biology, Okazaki, Japan
Abstract Text: Spermatogonial stem cells (SSCs) support continual spermatogenesis under homeostasis. Within the seminiferous tubules, SSCs both persist and produce committed progenitor cells in a spatiotemporally regulated manner. Subsequent differentiation follows a temporally periodic pattern, known as the “spermatogenic cycle”, forming a layered cellular arrangement. Along the tubule length, these stages are aligned in temporal sequence, creating the “spermatogenic wave”. At the macroscopic level, the stages are organized so that the wave propagates from both ends of the tubules connected to the rete testis, referred to as the “descent of segmental order.” Such trans-scale patterning underlies the robust and continuous sperm production.
Since the discovery of the cycle and wave in 1871, these dynamic patterns have drawn attention. Yet, their behaviors and underlying mechanisms remain underexplored, largely due to the lack of time-resolved observation methods. Here, using high-resolution, wide-field, and long-term live imaging (up to 10 days in vivo and one month ex vivo), we investigated how the behaviors of individual germ cells are organized into the cycle and wave. Our results show that the spermatogenic wave exhibits notable irregularities, including cycle-to-cycle variation. We also quantitatively mapped the descent of segmental order across entire seminiferous tubule loops (~20 cm each). Then, a minimal biophysical model of phase-coupled oscillators could recapitulate the intricate wave dynamics without invoking external cues. Finally, we found that interplay between SSCs and differentiating cells through retinoic acid metabolism can generate coupled oscillators that drive higher-order dynamics.
These findings suggest that the spermatogenic cycle, wave, and descent of segmental order emerge as self-organizing phenomena from the dynamic interplay between SSCs and differentiating cells.
