Lashley Lisa E E L O, Buurma Aletta, Swings Godelieve M J S, Eikmans Michael, Anholts Jacqueline D H, Bakker Jaap A, Claas Frans H J
Department of Gynecology and Obstetrics, Leiden University Medical Centre, The Netherlands.
Department of Pathology, Leiden University Medical Centre, The Netherlands.
J Reprod Immunol. 2015 Jun;109:17-23. doi: 10.1016/j.jri.2015.03.004. Epub 2015 Mar 30.
Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p < 0.03) higher incidence of C4d deposition was observed in placentas from women with preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p < 10th percentile) compared with the preeclamptic OD group. In addition, the placental mRNA expression level of complement regulatory proteins was significantly lower in uncomplicated and preeclamptic OD compared with the autologous pregnancies. In line with autologous preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies.
卵母细胞捐赠(OD)是一种特定的辅助生殖技术方法,在孕期发生子痫前期的风险较高。OD妊娠子痫前期的病理生理机制被认为与自体妊娠子痫前期不同。由于自体妊娠子痫前期被认为与补体激活有关,我们研究了子痫前期OD妊娠中的C4d沉积、循环补体成分和胎盘补体调节蛋白。选取了OD或自然受孕后妊娠过程顺利及发生子痫前期的女性。我们对胎盘进行C4d染色(补体激活的标志物),检测母体血清中的补体因子C1q、C3和C4,并对胎盘补体调节蛋白CD46、CD55和CD59的mRNA表达进行定量分析。与妊娠过程顺利的妊娠(包括OD和自体妊娠)相比,子痫前期女性胎盘的C4d沉积发生率显著更高(p < 0.03)。各研究组血清中的补体因子水平无差异。与子痫前期OD组相比,自体子痫前期组出生的儿童出生体重显著更低(p <第10百分位数)。此外,与自体妊娠相比,妊娠过程顺利及子痫前期OD妊娠的胎盘补体调节蛋白mRNA表达水平显著更低。与自体子痫前期妊娠一样,子痫前期OD妊娠中补体过度激活。然而,与自体妊娠不同的是,这与补体调节蛋白的代偿性上调无关。此外,OD妊娠中的C4d沉积与子痫前期的严重程度无关,提示子痫前期OD妊娠中胎盘C4d沉积存在另一种触发因素或调节机制。