Transfer RNA-derived small RNAs in female reproductive disorders: emerging roles and clinical implications

Female reproductive disorders present significant challenges worldwide. Transfer RNA-derived small RNAs (tsRNAs), a structurally diverse class of non-coding RNAs mainly comprising tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs), have emerged as key regulators in human health and disease. This review outlines the biogenesis and functions of tsRNAs and summarizes their mechanistic involvement and clinical implications across a range of reproductive pathologies. In pregnancy-related complications, such as embryo implantation failure and recurrent spontaneous abortion, aberrant tsRNA profiles perturb trophoblast behavior, endometrial decidualization, and maternal-fetal crosstalk, thereby compromising placental development and pregnancy outcome. In benign gynecological conditions including premature ovarian failure and endometriosis, dysregulated tsRNAs disrupt granulosa cell survival, promote stromal proliferation, and reshape inflammatory signaling, ultimately altering follicular development and uterine homeostasis. As our understanding of tsRNA-mediated pathways deepens, these molecules offer promising potential as diagnostic biomarkers and therapeutic targets for precision medicine in female reproductive disorders.