Single-cell RNA sequencing reveals the local cell landscape in mouse epididymal initial segment during aging.
Single-cell RNA sequencing reveals the local cell landscape in mouse epididymal initial segment during aging.
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DOI：
10.1186/s12979-023-00345-9
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发表时间：
2023-05-11
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影响因子：
--
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衰老生殖器官的形态和功能变化会导致男性生育力下降。附睾是睾丸后精子成熟的过渡区。我们先前已经证明，附睾起始段(IS)是精子成熟和获能所必需的生殖道区域，在小鼠衰老过程中经历了相当大的组织学变化和慢性免疫激活。然而，与衰老相关的附睾局部细胞和分子变化却知之甚少。我们对幼龄(3月龄)和老年(21月龄)小鼠的附睾体进行了单细胞RNA测序分析。总共从幼年和老年小鼠的附睾体组织中获得了10,027个细胞并进行了注释。细胞组成包括主细胞亚型和Ms4a4bHiMs4a6bHi T细胞随年龄的变化。衰老的主细胞表现出与顶体反应和精子成熟相关的多种功能基因表达的变化，提示附睾期精子的激活和成熟是一个不同步的过程。同时，在免疫细胞中发现了与衰老相关的改变途径，特别是Cx3cr1Hi附睾树突状细胞(EDCs)的“细胞趋化”。单核细胞特异性趋化因子CCL8的表达随着年龄的增长而增加。老年附睾炎性细胞浸润增多，细胞因子分泌增多。此外，细胞-细胞通讯分析表明，AGE增加了附睾炎性信号。与男性近端生殖道低免疫反应的一般模式相反，我们揭示了小鼠附睾起始段的炎症状态。这些发现将使未来的研究能够通过免疫调节来延缓男性生殖衰老。网上版载有补充材料，可在10.1186/s12979-023-00345-9查阅。
Morphological and functional alterations in aging reproductive organs result in decreased male fertility. The epididymis functions as the transition region for post-testicular sperm maturation. And we have previously demonstrated that the epididymal initial segment (IS), a region of the reproductive tract essential for sperm maturation and capacitation, undergoes considerable histological changes and chronic immune activation in mice during aging. However, the local aging-associated cellular and molecular changes in the aged epididymal IS are poorly understood. We conducted single-cell RNA sequencing analysis on the epididymal IS of young (3-month-old) and old (21-month-old) mice. In total, 10,027 cells from the epididymal IS tissues of young and old mice were obtained and annotated. The cell composition, including the expansion of a principal cell subtype and Ms4a4bHiMs4a6bHi T cells, changed with age. Aged principal cells displayed multiple functional gene expression changes associated with acrosome reaction and sperm maturation, suggesting an asynchronous process of sperm activation and maturation during epididymal transit. Meanwhile, aging-related altered pathways in immune cells, especially the “cell chemotaxis” in Cx3cr1Hi epididymal dendritic cells (eDCs), were identified. The monocyte-specific expression of chemokine Ccl8 increased with age in eDCs. And the aged epididymal IS showed increased inflammatory cell infiltration and cytokine secretion. Furthermore, cell–cell communication analysis indicated that age increased inflammatory signaling in the epididymal IS. Contrary to the general pattern of lower immune responses in the male proximal genital tract, we revealed an inflammaging status in mouse epididymal initial segment. These findings will allow future studies to enable the delay of male reproductive aging via immune regulation. The online version contains supplementary material available at 10.1186/s12979-023-00345-9.
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影响因子：
4.6
作者：
Drujont L;Lemoine A;Moreau A;Bienvenu G;Lancien M;Cens T;Guillot F;Bériou G;Bouchet-Delbos L;Fehling HJ;Chiffoleau E;Nicot AB;Charnet P;Martin JC;Josien R;Cuturi MC;Louvet C
通讯作者：
Louvet C
影响因子：
3.6
作者：
Johnston, DS;Jelinsky, SA;Turner, TT
通讯作者：
Turner, TT
DOI：
10.1111/j.1749-6632.2010.05700.x
发表时间：
2010-01-01
期刊：
REPRODUCTIVE AGING
影响因子：
--
作者：
Haaga, John;O'Connor, Kathleen;Wise, Phyllis
通讯作者：
Wise, Phyllis
DOI：
10.1530/rep-10-0493
发表时间：
2011-05
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Da Silva N;Cortez-Retamozo V;Reinecker HC;Wildgruber M;Hill E;Brown D;Swirski FK;Pittet MJ;Breton S
通讯作者：
Breton S
影响因子：
4.4
作者：
Leir, Shih-Hsing;Yin, Shiyi;Harris, Ann
通讯作者：
Harris, Ann