Spaceflight multi-omics reveals vulnerabilities of human germ cell development.

Abstract

Understanding the impact of spaceflight on human reproduction is critical for interplanetary exploration, yet technical barriers have limited direct studies of germ cell biology in orbit. Here, we utilized an automated bioreactor that supported long-term differentiation of human embryonic stem cells into human induced primordial germ cells (hiPGCs), human induced ovarian follicles (hiOFs), and human induced spermatogonial stem cells (hiSSCs) aboard spacecraft. Integrated real-time imaging, programmable medium perfusion, and in situ preservation enabled time-resolved multi-omics analysis. During missions on China's Tianzhou-1 and Tianzhou-6 spacecraft, spaceflight reduced hiPGC specification efficiency by approximately 50% and suppressed hiSSC proliferation by 26%. Transcriptome-translatome coordination revealed cell-type-specific dysregulation of extracellular matrix organization, microtubule dynamics, and lipid metabolism. Whole-exome sequencing and DNA methylome analysis demonstrated preserved genomic integrity despite these functional perturbations. These findings provide direct evidence that spaceflight perturbs human germ cell development and establish a scalable framework for monitoring cellular adaptation during deep-space missions.