Sperm enter glands of preovulatory bovine endometrial explants and initiate inflammation
Sperm enter glands of preovulatory bovine endometrial explants and initiate inflammation
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DOI：
10.1530/rep-19-0414
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发表时间：
2020-02-01
期刊：
影响因子：
3.8
通讯作者：
Miyamoto, Akio
中科院分区：
文献类型：
--
作者：
Akthar, Ihshan;Suarez, Susan S.;Miyamoto, Akio
我们之前报道过，精子与培养的牛子宫上皮细胞单层结合会诱导涉及 Toll 样受体 (TLR2) 信号通路的急性炎症反应。这种反应有助于清除子宫中的精子，从而为子宫内膜的植入做好准备。子宫内膜由表面上皮细胞排列；然而，上皮细胞也排列在子宫腺体上。为了研究免疫反应的来源，我们使用了外植体模型。将牛子宫内膜外植体与线粒体中 JC1 荧光标记照射的公牛精子一起孵育。精子在表面上皮上滑动，直到遇到并进入子宫腺体，并停留在那里。外植体的扫描电子显微镜显示子宫腺体中存在多形核中性粒细胞（PMN）和精子。在没有精子的情况下，腺体中看不到中性粒细胞。精子与外植体的孵育导致急性炎症反应，表现为整个外植体中 IL8、TNFA、IL1B、PGES 和 TLR2 mRNA 表达的上调，以及子宫腺体中 TNFA 蛋白表达的增加。 TLR1/2拮抗剂减少腺体中的精子数量并抑制TNFA的增加。我们的观察表明，子宫腺体是精子与子宫上皮相互作用的场所，触发先天免疫反应，从子宫清除多余的精子。
We previously reported that sperm binding to cultured monolayers of bovine uterine epithelial cells induces an acute inflammatory response involving the Toll-like receptor (TLR2) signaling pathway. This response serves to clear the uterus of sperm and thereby prepares the endometrium for implantation. The endometrium is lined by surface epithelial cells; however, epithelial cells also line uterine glands. To investigate the source of the immune response, we used an explant model. Explants of bovine endometrium were incubated with bull sperm illuminated by JC1 fluorescent labeling in their mitochondria. The sperm glided over the surface epithelium until they encountered and entered uterine glands, where they remained. Scanning electron microscopy of explants revealed polymorphonuclear neutrophils (PMNs) in uterine glands along with sperm. In the absence of sperm, PMNs were not seen in glands. The incubation of sperm with explants resulted in an acute inflammatory response, seen as the upregulation of mRNA expression of IL8, TNFA, IL1B, PGES and TLR2 in whole explants, as well as increased TNFA protein expression in uterine glands. TLR1/2 antagonist reduced sperm numbers in the glands and inhibited the increase of TNFA. Our observations suggest that uterine glands serve as a site where sperm interact with the uterine epithelium to trigger the innate immune response to clear excess sperm from the uterus.