A systematic review of microgravity on reproductive systems: Implications for space biology and human health

Microgravity poses risks to mammalian reproductive health by altering gametogenesis, fertilization, and embryonic development. This review summarizes evidence from spaceflight and ground-based microgravity analogs, together with radiation exposures, showing disruptions in spermatogenesis, oogenesis, and pre-implantation embryo development that depend on cell type, exposure duration, and experimental platform. Mechanistic studies indicate that microgravity and radiation can trigger oxidative stress, DNA damage, mitochondrial dysfunction, and epigenetic alterations, potentially reducing gamete quality and embryo viability. We also highlight extracellular vesicles as key mediators of gamete maturation, fertilization, and implantation; microgravity-related changes in EV biogenesis or cargo may further impair reproductive success. In addition, spaceflight-associated microbiome shifts-including emerging evidence on reproductive-tract microbiomes-may influence fertility via immune dysregulation and inflammation. Finally, we discuss countermeasures such as artificial gravity, dietary and antioxidant/radioprotective strategies, and reproductive technologies, and outline priorities for future research to safeguard reproductive health in space and advance reproductive medicine on Earth.