Reproductive Medicine Center, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan 471000, P.R. China.
Int J Oncol. 2018 Nov;53(5):1847-1856. doi: 10.3892/ijo.2018.4540. Epub 2018 Aug 28.
Preeclampsia (PE) in pregnancy is associated with vitrified-thawed embryo transfer. Pleiotrophin (PTN) is important in inflammation via its receptors. The aim of the present study was to determine the effect of PTN on the risk of PE following embryo transfer. An enzyme-linked immunosorbent assay was performed to determine the levels of tumor necrosis factor (TNF)-α and PTN in serum. The knockdown of PTN was conditionally induced by tamoxifen (tax) treatment. The tail-cuff method and Bradford assay were used to monitor blood pressure and the level of urine protein, respectively. The expression patterns of PTN, receptor protein tyrosine phosphatase β/ζ, (RPTPβ/ζ), syndecan-1 (SDC1), syndecan-3 (SDC3) and anaplastic lymphoma kinase (ALK) were determined by immunohistochemistry (IHC). Western blot analysis was performed to evaluate the expression level of PTN and its receptors. The risk of PE was elevated following embryo transfer in clinical and in the tax/PTN-/- group. It was found that the level of PTN increased when pregnancy progressed in normal conditions, however, the level of PTN was reduced in the PE mice. In addition, increases in TNF-α, blood pressure and urine protein were more marked in the PE mice that lacked PTN, compared with those in other PE mice. In addition, overlapping expression of PTN and its receptors in villous mesenchyme and fetal macrophages were identified using an IHC assay. However, the positive staining of PTN and its receptors was weaker or even absent in the PE mice. The protein level of RPTPβ/ζ was lower in the PE mice that lacked PTN than that in the other PE mice. The knockdown of PTN increased the risk of PE following vitrified-thawed embryo transfer, in which its receptors, particularly RPTPβ/ζ, may be involved.
妊娠子痫前期 (PE) 与玻璃化冷冻胚胎移植有关。多效蛋白 (PTN) 通过其受体在炎症中起重要作用。本研究旨在确定 PTN 对胚胎移植后发生 PE 的风险的影响。采用酶联免疫吸附试验测定血清中肿瘤坏死因子-α (TNF-α) 和 PTN 的水平。用他莫昔芬 (tax) 处理条件性诱导 PTN 敲低。尾套法和 Bradford 法分别用于监测血压和尿蛋白水平。通过免疫组织化学 (IHC) 检测 PTN、受体蛋白酪氨酸磷酸酶-β/ζ (RPTPβ/ζ)、连接蛋白-1 (SDC1)、连接蛋白-3 (SDC3) 和间变性淋巴瘤激酶 (ALK) 的表达模式。Western blot 分析用于评估 PTN 及其受体的表达水平。胚胎移植后临床和 tax/PTN-/-组的 PE 风险增加。结果发现，在正常情况下，随着妊娠的进展，PTN 的水平增加，但在 PE 小鼠中，PTN 的水平降低。此外，缺乏 PTN 的 PE 小鼠的 TNF-α、血压和尿蛋白水平升高更为明显，与其他 PE 小鼠相比。此外，通过 IHC 检测在绒毛间质和胎儿巨噬细胞中鉴定到 PTN 及其受体的重叠表达。然而，在 PE 小鼠中，PTN 及其受体的阳性染色较弱甚至缺失。缺乏 PTN 的 PE 小鼠中 RPTPβ/ζ 的蛋白水平低于其他 PE 小鼠。PTN 的敲低增加了玻璃化冷冻胚胎移植后发生 PE 的风险，其受体，特别是 RPTPβ/ζ，可能参与其中。
