Hirayama Hiroki, Sakumoto Ryosuke, Koyama Keisuke, Yasuhara Taichi, Hasegawa Taito, Inaba Ryo, Fujii Takashi, Naito Akira, Moriyasu Satoru, Kageyama Soichi
Department of Bioproduction, Graduate School of Bioindustry, Tokyo University of Agriculture, Hokkaido 099-2493, Japan.
Division of Animal Breeding and Reproduction Research, Institute of Livestock and Grassland Science, National Agriculture and Food Research Organization, Ibaraki 305-0901, Japan.
J Reprod Dev. 2020 Feb 14;66(1):49-55. doi: 10.1262/jrd.2019-113. Epub 2019 Nov 22.
In bovine placentomes, the inflammatory response is considered important for the detachment of the fetal membrane from the caruncle after parturition. Glucocorticoids, a trigger of the onset of parturition, facilitate functional maturation of placentomes via prostaglandin (PG) and estrogen production in cattle. This study investigated how exogeneous glucocorticoids, which exert immunosuppressive effects, affect placental inflammation at parturition. Placentomes were collected immediately after spontaneous or induced parturition. Parturition was conventionally induced using PGF2α or dexamethasone or with a combination of triamcinolone acetonide and high-dose betamethasone (TABET treatment). Polymerase chain reaction (PCR) array analysis indicated that 9/13 C-C motif chemokine ligands (CCLs) were upregulated > two-fold in spontaneous parturition, with CCL2 and CCL8 being highly expressed. The expressions of CCL2, CCL8, C-C motif chemokine receptor 1 (CCR1), and CCR5 in caruncles were significantly higher in spontaneous parturition than in induced parturition. Although the clinical dose of dexamethasone did not influence the expression of these CCLs and CCRs, TABET treatment increased CCR1 expression. CCL8, CCR1, CCR2, and CCR5 were localized in the caruncular epithelial cells. CCR2 was also localized in the epithelial cells of the cotyledonary villi. This study is the first report to reveal the disruption in CCL and CCR expression in bovine placentomes at induced parturition. Enhanced glucocorticoid exposure for the induction of parturition may upregulate CCR1 expression in placentomes, but the treatment does not adequately promote CCL expression. Additionally, immunohistochemistry suggested that the CCL-CCR system is involved in the functional regulation of maternal and fetal epithelial cells in placentomes at parturition.
在牛胎盘小叶中，炎症反应被认为对分娩后胎膜与肉阜的分离很重要。糖皮质激素是分娩开始的触发因素，它通过牛体内前列腺素（PG）和雌激素的产生促进胎盘小叶的功能成熟。本研究调查了具有免疫抑制作用的外源性糖皮质激素如何影响分娩时的胎盘炎症。在自然分娩或诱导分娩后立即收集胎盘小叶。传统上使用前列腺素F2α或地塞米松，或曲安奈德和高剂量倍他米松联合使用（TABET治疗）来诱导分娩。聚合酶链反应（PCR）阵列分析表明，在自然分娩中，13种C-C基序趋化因子配体（CCL）中有9种上调了两倍以上，其中CCL2和CCL8高表达。肉阜中CCL2、CCL8、C-C基序趋化因子受体1（CCR1）和CCR5的表达在自然分娩中显著高于诱导分娩。虽然临床剂量的地塞米松不影响这些CCL和CCR的表达，但TABET治疗增加了CCR1的表达。CCL8、CCR1、CCR2和CCR5定位于肉阜上皮细胞。CCR2也定位于子叶绒毛的上皮细胞。本研究首次揭示了诱导分娩时牛胎盘小叶中CCL和CCR表达的破坏。为诱导分娩而增加的糖皮质激素暴露可能上调胎盘小叶中CCR1的表达，但该治疗不能充分促进CCL的表达。此外，免疫组织化学表明CCL-CCR系统参与了分娩时胎盘小叶中母体和胎儿上皮细胞的功能调节。
