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

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This review details the biogenesis, functions, and emerging clinical roles of transfer RNA-derived small RNAs in female reproductive disorders, highlighting their involvement in pregnancy complications and gynecological conditions.

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This paper is a narrative review examining transfer RNA-derived small RNAs (tsRNAs), including tRNA halves (tiRNAs) and tRNA-derived fragments (tRFs), focusing on their biogenesis, regulatory functions, mechanistic roles, and potential clinical uses across female reproductive disorders. It reports that aberrant tsRNA profiles in pregnancy-related complications are linked to disrupted trophoblast behavior, impaired endometrial decidualization, and altered maternal–fetal signaling, while in benign gynecologic conditions such as premature ovarian failure and endometriosis they are associated with changes in granulosa cell survival, stromal proliferation, and inflammatory signaling that affect follicular development and uterine homeostasis. A key limitation is that, as a review, it synthesizes findings from heterogeneous studies rather than presenting new primary experimental data. Relevance to endometriosis: it explicitly discusses endometriosis as an example benign gynecological condition where dysregulated tsRNAs reshape inflammatory signaling and influence uterine homeostasis, though the paper’s main focus is a broad review of tsRNAs across multiple reproductive pathologies.

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Abstract

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.
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Abstract

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. Similar content being viewed by others Data availability Data were available from the corresponding author upon reasonable request.

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Biomed Res Int. 2022;2022:9911472. Chen Z, Zhao H, Fu N, Chen L. The diversified function and potential therapy of ectopic olfactory receptors in non-olfactory tissues. J Cell Physiol. 2018;233(3):2104–15. Park S, Ham J, Yang C, Park W, Park H, An G, et al. Melatonin inhibits endometriosis development by disrupting mitochondrial function and regulating tiRNAs. J Pineal Res. 2023;74(1):e12842. Zhou Q, He M, Liu M, Sun G, Li J. Emerging roles and therapeutic potential of tRNA-derived small RNAs in reproductive system diseases: a review. Front Cell Dev Biol. 2025;13:1698265. Funding This work was supported by the National Natural Science Foundation of China (82260315), Natural Science Foundation of Jiangxi Province (20242BAB25446), and Key Science and Technology Innovation Project of the Provincial Health Commission (2026ZD008). Author information Authors and Affiliations Contributions R.J., J.H., and J.Z. conceptualized the review topic and defined its scope. R.J. and Y.D. designed the literature search strategy and performed the literature search and study selection. R.J., L.Z., and J.C. synthesized and interpreted the literature. R.J. and Y.D. drafted the manuscript. Y.D. and H.C. prepared the figures and tables. Y.Z., J.H., and J.Z. critically revised the manuscript for intellectual content. J.H. and J.Z. supervised the work. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Ethics approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Jiang, R., Deng, Y., Zou, L. et al. Transfer RNA-derived small RNAs in female reproductive disorders: emerging roles and clinical implications. J Assist Reprod Genet (2026). https://doi.org/10.1007/s10815-026-03882-6 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s10815-026-03882-6

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