Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, MO, USA.
Am J Reprod Immunol. 2019 Nov;82(5):e13176. doi: 10.1111/aji.13176. Epub 2019 Aug 16.
Recent advances in lipid research have revealed that impairments in lipid mediator signaling can be involved in the pathoetiology of a variety of diseases. We previously reported aberrant expression of autotaxin, a key enzyme for lysophosphatidic acid (LPA) production, in placentas from women with preeclampsia. The present study aimed to further explore the involvement of LPA signaling in the pathoetiology of preeclampsia.
Term placentas were obtained from deliveries after uncomplicated pregnancy (n = 18) and those complicated by preeclampsia (n = 24). First-trimester placental tissues were collected after elective terminations of pregnancy (n = 20). Placental expression of the six identified LPARs (LPAR1-6) was analyzed at protein and mRNA levels.
In normal pregnancy, the mRNA expression levels of all LPARs except LPAR4 were significantly higher in term. Levels of mRNA encoding LPAR2-5 were significantly increased in preeclampsia placentas compared with those in the normal term placentas. Using Western immunoblotting, only LPAR3 was noted to be increased at the protein level in placentas from preeclamptic pregnancies. This was validated by immunohistochemistry.
In summary, the placental expression of LPARs, particularly LPAR3, is enhanced in preeclampsia, suggesting that disturbances in placental LPA signaling may be involved in the pathogenesis of preeclampsia.
最近的脂质研究进展表明，脂质介质信号的损伤可能与多种疾病的发病机制有关。我们之前报道过，先兆子痫患者的胎盘存在自分泌酶（autotaxin）表达异常，自分泌酶是产生溶血磷脂酸（LPA）的关键酶。本研究旨在进一步探讨 LPA 信号在先兆子痫发病机制中的作用。
从正常妊娠（n=18）和子痫前期（n=24）孕妇分娩的胎盘以及选择性终止妊娠的妊娠早期（n=20）胎盘获得组织。分析了 6 种已鉴定的 LPAR（LPAR1-6）在蛋白质和 mRNA 水平上的表达。
在正常妊娠中，除 LPAR4 外，所有 LPAR 的 mRNA 表达水平在足月时均显著升高。与正常足月胎盘相比，子痫前期胎盘中 LPAR2-5 的 mRNA 编码水平显著升高。通过 Western 免疫印迹，仅在子痫前期胎盘的蛋白水平上发现 LPAR3 增加，免疫组织化学验证了这一点。
总之，LPARs，特别是 LPAR3，在子痫前期的胎盘表达增强，表明胎盘 LPA 信号的紊乱可能与子痫前期的发病机制有关。
