衰老和巨噬细胞对小鼠睾丸间质干细胞增殖和分化的影响。
Effects of aging and macrophages on mice stem Leydig cell proliferation and differentiation .
机构信息
Zhejiang Provincial Key Laboratory of Anesthesiology, Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Key Laboratory of Children Genitourinary Diseases of Wenzhou City, Department of Pediatric Urology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
出版信息
Front Endocrinol (Lausanne). 2023 Mar 27;14:1139281. doi: 10.3389/fendo.2023.1139281. eCollection 2023.
BACKGROUND
Testosterone plays a critical role in maintaining reproductive functions and well-beings of the males. Adult testicular Leydig cells (LCs) produce testosterone and are generated from stem Leydig cells (SLCs) during puberty through adulthood. In addition, macrophages are critical in the SLC regulatory niche for normal testicular function. Age-related reduction in serum testosterone contributes to a number of metabolic and quality-of-life changes in males, as well as age-related changes in immunological functions. How aging and testicular macrophages may affect SLC function is still unclear.
METHODS
SLCs and macrophages were purified from adult and aged mice FACS using CD51 as a marker protein. The sorted cells were first characterized and then co-cultured to examine how aging and macrophages may affect SLC proliferation and differentiation. To elucidate specific aging effects on both cell types, co-culture of sorted SLCs and macrophages were also carried out across two ages.
RESULTS
CD51+ (weakly positive) and CD51++ (strongly positive) cells expressed typical SLC and macrophage markers, respectively. However, with aging, both cell types increased expression of multiple cytokine genes, such as IL-1b, IL-6 and IL-8. Moreover, old CD51+ SLCs reduced their proliferation and differentiation, with a more significant reduction in differentiation (2X) than proliferation (30%). Age matched CD51++ macrophages inhibited CD51+ SLC development, with a more significant reduction in old cells (60%) than young (40%). Crossed-age co-culture experiments indicated that the age of CD51+ SLCs plays a more significant role in determining age-related inhibitory effects. In LC lineage formation, CD51+ SLC had both reduced LC lineage markers and increased myoid cell lineage markers, suggesting an age-related lineage shift for SLCs.
CONCLUSION
The results suggest that aging affected both SLC function and their regulatory niche cell, macrophages.
背景
睾丸酮在维持男性生殖功能和健康方面起着关键作用。成年睾丸莱迪希细胞（LCs）产生睾丸酮，并在青春期到成年期期间由干细胞莱迪希细胞（SLCs）生成。此外，巨噬细胞对于正常睾丸功能的 SLC 调节龛位至关重要。与年龄相关的血清睾丸酮减少会导致男性许多代谢和生活质量的变化，以及与年龄相关的免疫功能变化。衰老和睾丸巨噬细胞如何影响 SLC 功能尚不清楚。
方法
使用 CD51 作为标记蛋白，通过 FACS 从小鼠的成年和老年组织中纯化 SLCs 和巨噬细胞。对分选细胞进行特征鉴定，然后进行共培养，以研究衰老和巨噬细胞如何影响 SLC 的增殖和分化。为了阐明特定的衰老对这两种细胞类型的影响，还在两个年龄段进行了分选 SLC 和巨噬细胞的共培养。
结果
CD51+（弱阳性）和 CD51++（强阳性）细胞分别表达典型的 SLC 和巨噬细胞标记物。然而，随着年龄的增长，两种细胞类型都增加了多种细胞因子基因的表达，如 IL-1b、IL-6 和 IL-8。此外，老年 CD51+ SLCs 的增殖和分化减少，分化减少更为显著（2 倍），而增殖减少仅为 30%。年龄匹配的 CD51++巨噬细胞抑制 CD51+ SLC 的发育，老年细胞（60%）比年轻细胞（40%）减少更为显著。交叉年龄共培养实验表明，CD51+ SLC 的年龄在决定与年龄相关的抑制作用方面起着更为重要的作用。在 LC 谱系形成中，CD51+ SLC 的 LC 谱系标记物减少，肌细胞谱系标记物增加，表明 SLC 存在与年龄相关的谱系转变。
结论
结果表明，衰老影响了 SLC 的功能及其调节龛位细胞巨噬细胞。
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