Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, 1737 Funako, Atsugi, Kanagawa, 243-0034, Japan.
NODAI Genome Research Center, Tokyo University of Agriculture, Setagaya, Tokyo, 156-8502, Japan.
Reprod Biol Endocrinol. 2017 Aug 14;15(1):63. doi: 10.1186/s12958-017-0284-z.
Endometrial cells secrete various cytokines and the dysfunction of endometrial cells may directly lead to infertility. Interferon tau (IFNT) secreted by trophoblast cells, a well-known pregnancy recognition signal in ruminants, acts on the uterus to prepare for pregnancy. Aging causes cellular and organ dysfunction, and advanced maternal age is associated with reduced fertility. However, few studies have investigated age-dependent changes in the uterus.
Using next generation sequencing and real-time PCR, we examined mRNA expression in bovine endometrial cells in vitro obtained from young (mean 45.2 months) and aged (mean 173.5 months) animals and the effects of IFNT depending on the age.
We showed that inflammation-related (predicted molecules are IL1A, C1Qs, DDX58, NFKB, and CCL5) and interferon-signaling (predicted molecules are IRFs, IFITs, STATs, and IFNs) pathways were activated in endometrial cells obtained from aged compared to young cows. Also, the activation of "DNA damage checkpoint regulation" and the inhibition of "mitotic mechanisms" in endometrial cells obtained from aged cows were evident. Moreover, we showed lower cell viability levels in endometrial cells obtained from aged compared to young cows. Although treatment with IFNT upregulated various types of interferon stimulated genes both in endometrial cells obtained from young and aged cows, the rate of increase by IFNT stimulus was obviously lower in endometrial cells obtained from aged compared to young cows.
Endometrial cells obtained from aged cows exhibited higher levels of inflammatory- and IFN-signaling, and dysfunction of cell division compared with young cows. In addition, a high basal level of IFN-related genes in endometrial cells of aged cows is suggested a concept of "inflammaging".
子宫内膜细胞分泌各种细胞因子，子宫内膜细胞功能障碍可能直接导致不孕。在反刍动物中，滋养层细胞分泌的干扰素 tau（IFNT）是一种众所周知的妊娠识别信号，作用于子宫为妊娠做准备。衰老导致细胞和器官功能障碍，而高龄产妇与生育能力下降有关。然而，很少有研究调查子宫随年龄的变化。
我们使用下一代测序和实时 PCR 检查了来自年轻（平均 45.2 个月）和高龄（平均 173.5 个月）动物的体外牛子宫内膜细胞中的 mRNA 表达，并研究了 IFNT 对年龄的影响。
我们表明，与年轻牛相比，高龄牛子宫内膜细胞中与炎症相关（预测分子为 IL1A、C1Qs、DDX58、NFKB 和 CCL5）和干扰素信号转导（预测分子为 IRFs、IFITs、STATs 和 IFNs）途径被激活。此外，高龄牛子宫内膜细胞中“DNA 损伤检查点调节”的激活和“有丝分裂机制”的抑制是明显的。而且，我们表明来自高龄牛的子宫内膜细胞的细胞活力水平较低。尽管 IFNT 处理上调了来自年轻和高龄牛的子宫内膜细胞中各种类型的干扰素刺激基因，但 IFNT 刺激引起的增加率在高龄牛的子宫内膜细胞中明显低于年轻牛。
与年轻牛相比，来自高龄牛的子宫内膜细胞表现出更高水平的炎症和 IFN 信号转导，以及细胞分裂功能障碍。此外，高龄牛子宫内膜细胞中 IFN 相关基因的高基础水平提示了“炎症衰老”的概念。
