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首页> 外文期刊>Reviews of Reproduction >Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep
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Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

机译：TLR7和TLR8参与绵羊的胎盘发育和妊娠的建立

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Toll-like receptors (TLRs) belong to the innate immune system and regulate inflammatory events that affect mammalian reproduction. In Study 1, we demonstrated that abundance of ovine TLR1–TLR9 mRNAs in the uterus differs due to reproductive status (TLR2, TLR3, TLR7, and TLR8) and the day of the estrous cycle and pregnancy (TLR1–TLR3, TLR5–TLR7, and TLR9). Expression of TLR7 and TLR8 proteins was localized primarily to uterine epithelia and stroma and regulated in a temporal manner. In Study 2, we determined that ovine conceptuses express TLR7 and TLR8 on all days studied and that expression of the envelope protein of ovine endogenous retrovirus (enJSRV-Env) declined in conceptus trophectoderm from Day 13 to Day 16 of pregnancy. In Study 3, loss-of-function experiments were conducted in vivo using morpholino antisense oligonucleotides (MAOs) injected into the uterine lumen to block synthesis of TLR7 and TLR8 proteins, individually and jointly. Conceptuses were recovered on Day 16 to assess their morphology. MAO-treated conceptuses were developmentally retarded, produced less interferon tau (IFNT), and had fewer binucleate cells (BNCs) compared with MAO-Controls. Moreover, expression of enJSRV-Env mRNA in MAO-TLR7 conceptuses was greater than that for MAO-Control and MAO-TLR8 conceptuses, but similar to MAO-TLR7/TLR8 conceptuses. Results of this study indicated differences in TLR1–TLR9 expression due to reproductive status and the day of the estrous cycle and pregnancy. TLR7 and TLR8 also influence development, enJSRV-Env abundance, secretion of IFNT, and formation of BNCs by conceptuses. These findings corroborate our hypothesis that TLR7 and TLR8 mediate pathways whereby enJSRV-Env regulates key peri-implantation events in conceptus development and differentiated functions of trophectoderm cells.
机译：Toll样受体（TLR）属于先天免疫系统，并调节影响哺乳动物繁殖的炎症事件。在研究1中，我们证明了子宫中绵羊TLR1-TLR9 mRNA的丰度因生殖状态（TLR2，TLR3，TLR7和TLR8）以及发情周期和妊娠日（TLR1-TLR3，TLR5-TLR7，和TLR9）。 TLR7和TLR8蛋白的表达主要定位于子宫上皮和间质，并以时间方式调节。在研究2中，我们确定从怀孕的第13天到第16天，绵羊概念动物在所有研究的天中都表达TLR7和TLR8，而绵羊内源性逆转录病毒（enJSRV-Env）包膜蛋白的表达在概念性滋养外胚层中下降。在研究3中，使用注入子宫腔的吗啉代反义寡核苷酸（MAO）在体内进行功能丧失实验，以单独和共同阻断TLR7和TLR8蛋白的合成。在第16天恢复了概念的形态，以评估其形态。与MAO-Controls相比，MAO治疗的概念动物发育迟缓，产生的干扰素tau（IFNT）更少，并且双核细胞（BNC）更少。此外，enJSRV-Env mRNA在MAO-TLR7概念中的表达高于MAO-Control和MAO-TLR8概念中的表达，但与MAO-TLR7 / TLR8概念中的表达相似。这项研究的结果表明，由于生殖状况以及动情周期和怀孕的天数，TLR1-TLR9表达存在差异。 TLR7和TLR8还影响概念的发育，enJSRV-Env丰度，IFNτ的分泌以及BNC的形成。这些发现证实了我们的假说，即TLR7和TLR8介导enJSRV-Env调节概念发育和滋养外胚层细胞功能分化过程中的关键植入期事件。

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