Seminal Plasma and Seminal Plasma Exosomes of Aged Male Mice Affect Early Embryo Implantation via Immunomodulation.
Seminal Plasma and Seminal Plasma Exosomes of Aged Male Mice Affect Early Embryo Implantation via Immunomodulation.
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DOI：
10.3389/fimmu.2021.723409
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yao B
中科院分区：
文献类型：
--
作者：
Wang D;Jueraitetibaike K;Tang T;Wang Y;Jing J;Xue T;Ma J;Cao S;Lin Y;Li X;Ma R;Chen X;Yao B
精浆（SP），特别是 SP 外泌体（sExos），会随着年龄的增长而改变，并可能影响雌性小鼠子宫免疫微环境。然而，高龄男性生育力下降与 SP 和 sExos 年龄相关变化（可能损害子宫免疫微环境）之间的关系仍不清楚。本研究表明，接受生殖年长雄性小鼠 SP 治疗的雌性小鼠（老年 SP 组）的着床率低于接受年轻雄性小鼠 SP 治疗的雌性小鼠（年轻 SP 组）的着床率。 RNA测序分析显示，与后一组相比，前一组的子宫中树突状细胞（DC）相关细胞因子和趋化因子的水平发生了变化。体内和体外实验表明，刺激后，老化的SP对DC成熟的抑制作用弱于年轻的SP。在分离和表征年轻和高龄雄性小鼠的 sExos 后，我们发现，用年轻雄性小鼠的 sExos 对老年 SP 组的子集进行授精，可以部分恢复着床率下降的情况。其他体内和体外实验表明，从老年雄性小鼠中提取的 sExos 对 DC 成熟的影响与老年小鼠的 SP 相似，表明与年龄相关的 sExos 抑制作用。总之，我们的研究表明，与年轻 SP 组相比，年龄相关的 sExos 改变可能是老年 SP 组着床率较低的部分原因，这是由子宫免疫调节介导的。这些发现为临床精液辅助治疗提供了新的见解。
Seminal plasma (SP), particularly SP exosomes (sExos), alters with age and can affect female mouse uterine immune microenvironment. However, the relationship between fertility decline in reproductively older males, and SP and sExos age-related changes, which may compromise the uterine immune microenvironment, remains unclear. The present study demonstrated that the implantation rate of female mice treated with SP from reproductively older male mice (aged-SP group) was lower than that of those treated with SP from younger male mice (young-SP group). RNA-sequencing analysis revealed altered levels of dendritic cell (DC)-related cytokines and chemokines in the uteri of the former group compared with those of the latter group. In vivo and in vitro experiments demonstrated a weaker inhibitory effect of aged SP on DC maturation than of young SP upon stimulation. After isolating and characterizing sExos from young and advanced-age male mice, we discovered that insemination of a subset of the aged-SP group with sExos from young male mice partially recovered the implantation rate decline. Additional in vivo and in vitro experiments revealed that sExos extracted from age male mice exerted a similar effect on DC maturation as SP of aged mice, indicating an age-related sExos inhibitory effect. In conclusion, our study demonstrated that age-related alterations of sExos may be partially responsible for lower implantation rates in the aged-SP group compared with those in the young-SP group, which were mediated by uterine immunomodulation. These findings provide new insights for clinical seminal adjuvant therapy.