The Recurrent Pregnancy Loss Unit, the Capital Region, Copenhagen University Hospitals, Rigshospitalet and Hvidovre Hospital, Kettegård Alle 30, Hvidovre 2650, Denmark; The Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen 2100, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University, Blegdamsvej 3B, Copenhagen 2200, Denmark.
The Department of Occupational and Environmental Medicine, Copenhagen University Hospital, Bispebjerg Hospital, Bispebjerg Bakke 23F, Copenhagen 2400, Denmark.
J Reprod Immunol. 2024 Jun;163:104221. doi: 10.1016/j.jri.2024.104221. Epub 2024 Feb 27.
The poor remodeling of placental spiral arteries seen in preeclampsia is also discussed to contribute to recurrent pregnancy loss (RPL) preceded by abnormal angiogenesis and excessive complement activation. Low levels of Mannose-binding-lectin (MBL), a pattern recognition molecule (PRM) of the lectin pathway, have been found in women with RPL. We propose that pregnancy loss is connected to defective angiogenesis with reperfusion damage in the placenta and decreased levels of PRM in the lectin pathway in women with RPL. In this cohort study, we investigate the angiogenic factors and the lectin complement pathway in early pregnancy and their time-dependent relationship with pregnancy outcomes in 76 women with secondary RPL (sRPL) who have at least four prior pregnancy losses and a live birth. We evaluated levels of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Vascular Endothelial Growth Factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PRMs, MBL, ficolin-1, -2, -3 and an additional soluble PRM, Pentraxin-3, during the 5th, 6th, and 7th gestational weeks. Our results showed that, compared to live births, pregnancies that ended in loss were associated with elevated VEGF levels and decreased levels of the Ang-2/Ang-1 ratio. Also, increasing levels of ficolin-2 were significantly associated with pregnancy loss, with MBL showing no association. Our research suggests that women with sRPL may have inadequate placentation with impaired angiogenesis in pregnancies ending in a loss.
在子痫前期中观察到的胎盘螺旋动脉重塑不良也被认为导致了反复妊娠丢失(RPL),这是由异常血管生成和过度补体激活引起的。在 RPL 女性中发现甘露糖结合凝集素(MBL)水平降低,MBL 是凝集素途径的模式识别分子(PRM)。我们提出,妊娠丢失与胎盘再灌注损伤中的血管生成缺陷有关,并且 RPL 女性的凝集素途径中的 PRM 水平降低。在这项队列研究中,我们研究了 76 名继发性 RPL(sRPL)女性在早期妊娠中的血管生成因子和凝集素补体途径及其与妊娠结局的时间依赖性关系,这些女性至少有四次妊娠丢失和一次活产。我们评估了血管生成素-1(Ang-1)、血管生成素-2(Ang-2)、血管内皮生长因子(VEGF)、可溶性 fms 样酪氨酸激酶-1(sFlt-1)和 PRM,即甘露糖结合凝集素(MBL)、ficolin-1、-2、-3 以及另外一种可溶性 PRM,Pentraxin-3 在第 5、6 和 7 孕周的水平。我们的结果表明,与活产相比,导致妊娠丢失的妊娠与 VEGF 水平升高和 Ang-2/Ang-1 比值降低有关。此外,ficolin-2 水平的升高与妊娠丢失显著相关,而 MBL 则没有关联。我们的研究表明,sRPL 女性的胎盘可能存在不足,导致妊娠丢失的妊娠中血管生成受损。