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