Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Placenta. 2010 Mar;31(3):222-9. doi: 10.1016/j.placenta.2009.12.009. Epub 2010 Jan 4.
Common complications of pregnancy arise in part from dysfunctional placental development, and include gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia (PE). Peroxisome proliferator-activated receptors (PPARs), and their partner retinoid X receptor a (RXRalpha), mediate trophoblast differentiation and thus may offer insight into the pathophysiology of these diseases.
Human placentae were obtained from women at term with GDM and were compared to uncomplicated term placentae. Placentae from women who delivered preterm with IUGR, PE or co-existing PE and IUGR were compared to matched controls. Quantitative RT-PCR and Western blotting were used to examine mRNA and protein expression of PPARalpha, PPARdelta, PPARgamma and RXRalpha. DNA binding activity of PPAR isoforms were measured in nuclear protein extracts.
GDM was associated with significantly lower placental PPARgamma mRNA and protein, PPARalpha protein and RXRalpha protein expression, while PPAR DNA binding activity remained unchanged. Placentae from women with PE did not demonstrate any changes in mRNA or protein expression or PPAR DNA binding activity, while IUGR/PE placenta showed significant increases in PPARalpha protein, PPARgamma mRNA and protein and RXRalpha mRNA and protein expression. Significantly elevated protein expression of PPARalpha and RXRalpha were associated with IUGR placentae. IUGR and IUGR/PE placentae had significantly higher PPARgamma DNA binding activity compared to controls.
The data presented herein suggest that PPARs may be involved in the pathophysiology of GDM, PE and IUGR.
妊娠的常见并发症部分源于胎盘功能障碍的发育，包括妊娠糖尿病（GDM）、宫内生长受限（IUGR）和子痫前期（PE）。过氧化物酶体增殖物激活受体（PPARs）及其配体视黄酸 X 受体 a（RXRalpha）介导滋养层细胞分化，因此可能深入了解这些疾病的病理生理学。
从患有 GDM 的足月妇女中获得人胎盘，并与无并发症的足月胎盘进行比较。将患有 IUGR、PE 或同时患有 PE 和 IUGR 的早产妇女的胎盘与匹配的对照组进行比较。使用定量 RT-PCR 和 Western blotting 检测 PPARalpha、PPARdelta、PPARgamma 和 RXRalpha 的 mRNA 和蛋白表达。在核蛋白提取物中测量 PPAR 同工型的 DNA 结合活性。
GDM 与胎盘 PPARgamma mRNA 和蛋白、PPARalpha 蛋白和 RXRalpha 蛋白表达显著降低有关，而 PPAR DNA 结合活性保持不变。PE 患者的胎盘未显示 mRNA 或蛋白表达或 PPAR DNA 结合活性的任何变化，而 IUGR/PE 胎盘则显示 PPARalpha 蛋白、PPARgamma mRNA 和蛋白以及 RXRalpha mRNA 和蛋白表达显著增加。IUGR 胎盘与 PPARalpha 和 RXRalpha 蛋白表达显著升高有关。IUGR 和 IUGR/PE 胎盘与对照组相比，PPARgamma DNA 结合活性显著升高。
本文提供的数据表明，PPARs 可能参与 GDM、PE 和 IUGR 的病理生理学。
