Knockdown of pleiotrophin increases the risk of preeclampsia following vitrified-thawed embryo transfer

摘要

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.