A testicular microfluidic organ-on-a-chip for mimicking spermatogenic epithelium.

The testicular spermatogenic epithelium, the fundamental functional unit of spermatogenesis, comprises Sertoli cells and a sequence of spermatogenic cells, with the Leydig cells (LCs) playing a pivotal supporting role in sperm development. In this study, we developed a microfluidic testicular organ-on-a-chip (OoC) composed of spermatogonial stem cells, Sertoli cells, and LCs. After 28 d of culture, the testicular OoC demonstrated the formation of a spermatogenic epithelial structure, with observed proliferation and differentiation of spermatogonial stem cells. Both Sertoli and LCs were noted to perform their fundamental cellular functions and engage in intercellular communication. Applying reproductive toxicity factors to testicular OoC reduced the proliferation of spermatogonia stem cell in the chip. This testicular OoC model revealed its potential for exploring physiological functions of the testicular spermatogenic epithelium and serving as a platform for pharmacological and toxicological screening.