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journal article·2026-07-21Open access

Super‐Multiplexed Label‐Free Raman Imaging Uncovers Novel Testicular Metabolic Couplings for Residual Body and Spermatogonial Differentiation

Jiaxin Li, Xia Chen, Yujuan Qi, Chen Qiao, Qiuru Huang, Dan Zhao, Weiyi Qian, Li Di, Yi Shi, Xiangqi Hu, Yueyue Shao, Kehan Wang, Zhiyu Tang‐Yang, Hanzhi Zang, Yuwen Du, Anran Dong, Jinxiong Feng, Jiayun Chen, Ying Zheng, Xiaofang Tan, Xiaoyu Zhao, Zhonghua Shi, Bo Zheng, Jun Yu

Advanced Science
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Abstract

ABSTRACT The biochemical composition underlying cytoplasmic residual body (RB) and arrested spermatogonia remains unresolved in spermatogenesis, in part due to limited approaches for intact‐tissue metabolic interrogation. Here we develop Super‐multiplexed Label‐free Raman Imaging (SLRI) to generate 2D/3D biochemical maps of intact Drosophila testes. SLRI delineates major testicular cell types and provides the first in situ, stage‐resolved mapping of cytoplasmic RBs at two discrete phases. We further identify a differentiation‐arrest‐associated metabolic trajectory in spermatogonial clusters, characterized by coordinated spatiotemporal decay of specific biochemical species. Across 42 spatiotemporally variant metabolites and metabolic pathways, SLRI reveals RB‐ and arrest‐enriched signatures. Notably, RBs and arrested spermatogonia display significant biochemical overlap, alongside unique spectral signatures. Furthermore, we uncovered a ring‐like, punctate arrangement of lipids, amino acids, and vitamins encircling RBs, suggesting structured metabolite partitioning during cytoplasmic remodeling. Collectively, SLRI establishes a general framework for high‐dimensional metabolic mapping and remodeling analysis in intact tissues.
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Research context

OpenAlex topics: Spectroscopy Techniques in Biomedical and Chemical Research · Sperm and Testicular Function · Advanced Fluorescence Microscopy Techniques

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Clinical Research Center for Reproductive Genetics Center for Reproductive Medicine Affiliated Maternity and Child Health Care Hospital of Nantong University Medical School of Nantong University Nantong China

Institute of Reproductive Medicine Medical School Nantong University Nantong China

Center for Reproductive Medicine, Affiliated Hospital of Nantong University Medical School of Nantong University Nantong China

Department of Reproductive Medicine Xuzhou Central Hospital Xuzhou Central Hospital affiliated to Southeast University Xuzhou Clinical School of Xuzhou Medical University Xuzhou China

Department of Clinical Pharmacy Affiliated Hospital of Jiangsu University Jiangsu University Zhenjiang China

Reproductive Medicine Center Reproductive Sciences Institute The Fourth Affiliated Hospital of Jiangsu University Jiangsu University Zhenjiang China

Changzhou Medical Center Changzhou Maternal and Child Health Care Hospital Nanjing Medical University Changzhou China

State Key Laboratory of Reproductive Medicine and Offspring Health Center For Reproduction and Genetics The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital Gusu School Nanjing Medical University Suzhou China

Department of Histology & Embryology Faculty of Medicine Yangzhou University Yangzhou China

SuperVision Medicine Co,.Ltd Wuxi China

Funding

National Natural Science Foundation of China

References (45)

Show source-provided references
1. A Comparison of Spermatogenesis Between Flies and Men‐Conserved Processes of Male Gamete Production10.1093/humupd/dmaf018 ↗
2. 10.1007/s00018‐025‐05831‐510.1007/s00018‐025‐05831‐5 ↗
3. 10.1186/s11658‐025‐00737‐310.1186/s11658‐025‐00737‐3 ↗
4. 10.1016/j.mce.2024.11227810.1016/j.mce.2024.112278 ↗
5. 10.1038/s41419‐021‐03783‐910.1038/s41419‐021‐03783‐9 ↗
6. Cyst Stem Cell Lineage eIF5 Non‐Autonomously Prevents Testicular Germ Cell Tumor Formation via eIF1A/eIF2γ‐Mediated Pre‐Initiation Complex10.1186/s13287-022-03025-5 ↗
7. 10.1038/s41420‐021‐00452‐w10.1038/s41420‐021‐00452‐w ↗
8. 10.1016/j.redox.2023.10267110.1016/j.redox.2023.102671 ↗
9. 10.1073/pnas.200048211910.1073/pnas.2000482119 ↗
10. 10.1093/biolre/ioaf09210.1093/biolre/ioaf092 ↗
11. 10.1002/jbio.20140006210.1002/jbio.201400062 ↗
12. 10.3791/6187010.3791/61870 ↗
13. 10.1038/nature2205110.1038/nature22051 ↗
14. 10.1016/j.abb.2024.10995010.1016/j.abb.2024.109950 ↗
15. 10.1186/s40659‐025‐00652‐z10.1186/s40659‐025‐00652‐z ↗
16. 10.1002/jmor.2132310.1002/jmor.21323 ↗
17. 10.1530/REP‐25‐029710.1530/REP‐25‐0297 ↗
18. 10.1242/jcs.0243010.1242/jcs.02430 ↗
19. 10.1530/REP‐09‐029810.1530/REP‐09‐0298 ↗
20. 10.1016/j.stemcr.2016.11.00710.1016/j.stemcr.2016.11.007 ↗
21. 10.1007/s42977‐022‐00122‐710.1007/s42977‐022‐00122‐7 ↗
22. Copper Homeostasis and Copper‐induced Cell Death in the Pathogenesis o f Cardiovascular Disease and Therapeutic Strategies10.1038/s41419-023-05639-w ↗
23. 10.1016/j.cell.2014.12.01910.1016/j.cell.2014.12.019 ↗
24. 10.1038/s41586‐025‐09616‐510.1038/s41586‐025‐09616‐5 ↗
25. 10.1369/0022155421105524010.1369/00221554211055240 ↗
26. Mimicking Exogenous Amino Acids: Raman‐based and Machine Learning Trac King of Colon Cancer Cells Metabolism10.1016/j.jphotobiol.2025.113285 ↗
27. 10.1021/acs.biochem.5c0023110.1021/acs.biochem.5c00231 ↗
28. 10.3390/molecules2801013710.3390/molecules28010137 ↗
29. 10.1016/j.biopha.2017.08.13110.1016/j.biopha.2017.08.131 ↗
30. 10.1530/jrf.0.088005110.1530/jrf.0.0880051 ↗
31. 10.1016/j.stemcr.2018.01.00310.1016/j.stemcr.2018.01.003 ↗
32. 10.3389/fcell.2022.83375910.3389/fcell.2022.833759 ↗
33. Retinoid Signaling Controls Spermatogonial Differentiation by Regulating Expression of Replication‐Dependent Core Histone Genes
34. 10.1210/en.2011‐110210.1210/en.2011‐1102 ↗
35. 10.1146/annurev‐biochem‐091724‐01373310.1146/annurev‐biochem‐091724‐013733 ↗
36. 10.1016/j.celrep.2025.11640610.1016/j.celrep.2025.116406 ↗
37. 10.1126/science.abj664710.1126/science.abj6647 ↗
38. Cellular Fate of Intersex Differentiation10.1038/s41419-021-03676-x ↗
39. 10.1021/acs.langmuir.4c0506310.1021/acs.langmuir.4c05063 ↗
40. Advances in Non‐Thermal Processing of Meat and Monitoring Meat Protein Gels Through Vibrational Spectroscopy10.3390/foods14111929 ↗
41. 10.1016/S0022‐2275(20)41186‐110.1016/S0022‐2275(20)41186‐1 ↗
42. 10.1002/adhm.20240103210.1002/adhm.202401032 ↗
43. ECM characterization and 3D Bioprinted Models of NSCLC for Investigating Stiffness‐Dependent Tumor Behavior and Drug Response10.1016/j.mtbio.2025.101823 ↗
44. 10.1016/j.crmeth.2023.10044010.1016/j.crmeth.2023.100440 ↗
45. 10.1038/s41566‐025‐01707‐z10.1038/s41566‐025‐01707‐z ↗