PubMed · 42379502
Integrating transcriptomics and metabolomics reveals the molecular landscape of sperm maturation driven by regional differentiation in the epididymis of Guizhou-Guiqian semi-fine wool sheep.
Abstract
Epididymal regionalized differentiation is crucial for sperm maturation. However, little is known about the synergistic remodeling mechanisms of different epididymal segments at the transcriptional and metabolic levels during sexual maturation in ruminants (especially sheep). We investigated the caput, corpus, and cauda epididymidis of pre-pubertal (2-month-old) and post-pubertal (7-month-old) Guizhou-Guiqian semi-fine wool sheep using histology, RNA sequencing, and metabolomics. Post-pubertal tissues exhibited increased luminal diameters, cilia lengths, and abundant cauda spermatozoa. Transcriptomic analysis revealed increasing differentially expressed genes (DEGs) along the caput-corpus-cauda axis (4642, 6103, and 7698 DEGs, respectively). Metabolomics detected 786 unique differentially accumulated metabolites (DAMs). Region-specific analysis showed that in the caput, up-regulated pathways (fructose/mannose metabolism; HK2, ALDOA, HKDC1) provide energy and substrates for initial sperm motility. In the corpus, down-regulated genes associated with extracellular matrix and tight junctions suggested epithelial barrier remodeling to establish an immune-tolerant microenvironment. The cauda specifically up-regulated the pentose phosphate pathway (FBP1, GPI) and glutathione metabolism, maintaining redox homeostasis for long-term sperm storage. Additionally, glycerophospholipid metabolism was enriched across all segments, where PEMT, AGPAT5, and LCAT likely regulate sperm plasma membrane fluidity. In conclusion, during sexual maturation, the caput drives energy metabolism and glycosylation, the corpus establishes immune tolerance, and the cauda maintains antioxidant homeostasis. The glycerophospholipid network throughout the across all epididymal segments synergistically remodels sperm membrane. This study reveals the underlying multi-omics regulatory mechanisms of epididymal functional differentiation, providing a theoretical basis for elucidating the molecular mechanisms of sperm maturation in this breed and for the molecular breeding of early reproductive performance in rams.
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Xujie Li, Huihui Wang, Xiaodan Shi, Ling Pu, Haolin Chen, Taotao Li. 2026-06-30. Integrating transcriptomics and metabolomics reveals the molecular landscape of sperm maturation driven by regional differentiation in the epididymis of Guizhou-Guiqian semi-fine wool sheep.. https://doi.org/10.1016/j.ygeno.2026.111288
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