The phenomenon of aging arises from multiple, complex interactions causing dysfunction in cells and organs. In particular, fertility drastically decreases with age. Previously, we have demonstrated that the functional characteristics of the bovine oviduct and uterus change with the age-dependent upregulation of inflammation and noted that S100A9 triggers inflammatory responses in oviduct epithelial cells. In the present study, we investigated the hypothesis that S100A9 affects reproductive events to aspect such as sperm function, fertilization, and the development of the embryo in cows. To investigate the effect of S100A9 on bovine sperm, we incubated sperms in vitro with S100A9 for 5 h and observed significantly decreased sperm motility and viability. During in vitro fertilization, S100A9 treatment for 5 h did not affect the rate of fertilization, time of first division of embryos, or embryo development to blastocyst stage. Treatment of 2-cell stage embryos with S100A9 for 5 h significantly reduced the proportion of cells undergoing normal division (4-8 cell embryos) and embryo development to the blastocyst stage. In experiment involving 24 h treatment of 2-cell embryos, the development of all embryos stopped at the 2-cell stage in the S100A9-treated group. In blastocyst-stage embryos, S100A9 treatment significantly stimulated the expression of endoplasmic reticulum (ER) and the mRNA expression of ER stress markers, and activated caspase-3 with subsequent nuclear fragmentation. Pre-treatment with an ER stress inhibitor significantly suppressed caspase-3 activation by the S100A9 treatment, suggesting that S100A9 induces blastocyst dysfunction by apoptosis (via caspase-3 activation) depending on ER stress. These results indicate that direct exposure to S100A9 exerted adverse effects on sperm function and embryo development. These findings suggest that excessive dose of S100A9 may have an adverse effect to the reproductive machinery by inducing inflammation and tissue dysfunction.

中文翻译：

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S100A9对牛精子的不利生殖作用和体外早期胚胎发育。

衰老现象源于多种复杂的相互作用，导致细胞和器官功能障碍。特别是，随着年龄的增长，生育能力急剧下降。以前，我们已经证明了牛输卵管和子宫的功能特性会随着年龄的炎症上调而改变，并注意到S100A9会触发输卵管上皮细胞的炎症反应。在本研究中，我们调查了S100A9影响生殖事件的假设，例如精子功能，受精和奶牛胚胎发育。为了研究S100A9对牛精子的作用，我们在体外将精子与S100A9一起温育了5小时，并观察到精子的活力和活力显着降低。在体外受精期间，S100A9处理5 h不会影响受精率，胚胎第一次分裂的时间，或胚胎发育到胚泡期。用S100A9处理2个细胞阶段的胚胎5小时，可显着减少经历正常分裂的细胞（4-8个细胞的胚胎）和胚胎发育到胚泡阶段的比例。在涉及24小时处理2细胞胚胎的实验中，在S100A9处理组中，所有胚胎的发育都在2细胞阶段停止。在胚泡期胚胎中，S100A9处理可显着刺激内质网（ER）的表达和ER应激标志物的mRNA表达，并激活caspase-3并随后发生核分裂。用ER应激抑制剂进行的预处理通过S100A9处理显着抑制了caspase-3的活化，提示S100A9依赖于内质网应激，通过凋亡（通过caspase-3激活）诱导胚泡功能障碍。这些结果表明直接暴露于S100A9对精子功能和胚胎发育产生不利影响。这些发现表明过量的S100A9可能通过诱导炎症和组织功能障碍而对生殖机械产生不利影响。