Molecular and Clinical Sciences Research InstituteSt. George's, University of London, London, UK.
Fetal Medicine UnitSt. George's Hospital, London, UK.
J Mol Endocrinol. 2018 Apr;60(3):239-246. doi: 10.1530/JME-17-0243. Epub 2018 Feb 7.
Successful implantation and placentation are dependent on the interaction between decidual stromal cells (DSC) and extravillous trophoblast (EVT) cells. The extent of trophoblast invasion relies on communication between the placenta and maternal decidua. The cyclical process of decidualisation induces a transformation of endometrial fibroblasts to secretory DSC; these secreted products have many functions including the control of trophoblast invasion. Inadequate trophoblast invasion and remodelling of the uterine vessels (the spiral arteries) are associated with pregnancy disorders such as pre-eclampsia. Uterine artery Doppler resistance index (RI) in the first trimester of pregnancy can be used as a proxy measure of remodelling. DSC were isolated from pregnancies with normal (normal RI) or impaired (high RI) spiral artery remodelling. Following isolation, DSC were re-decidualised using cAMP and MPA and secretion of the decidualisation markers IGFBP-1 and prolactin assessed. We examined the impact of DSC-secreted factors on trophoblast cell function, using the EVT cell line SGHPL-4. We demonstrated that DSC exposed to decidual factors were able to re-decidualise and that the chemoattraction of trophoblasts by DSC is impaired in pregnancies with high RI. This study provides new insights into the role that DSC play in regulating EVT functions during the first trimester of pregnancy. This is the first study to demonstrate that DSC from pregnancies with impaired vascular remodelling in the first trimester secrete factors that inhibit the directional movement of trophoblast cells. This finding may be important in understanding aberrant trophoblast invasion in pregnancies where vascular remodelling is impaired.
成功的着床和胎盘形成依赖于蜕膜基质细胞（DSC）和绒毛外滋养层（EVT）细胞之间的相互作用。滋养细胞的侵袭程度依赖于胎盘和母体蜕膜之间的通讯。蜕膜化的周期性过程诱导子宫内膜成纤维细胞向分泌型 DSC 的转化；这些分泌产物具有许多功能，包括控制滋养细胞的侵袭。滋养细胞侵袭不足和子宫血管（螺旋动脉）重塑不良与子痫前期等妊娠疾病有关。妊娠早期子宫动脉多普勒阻力指数（RI）可作为血管重塑的替代指标。我们从螺旋动脉重塑正常（正常 RI）或受损（高 RI）的妊娠中分离出 DSC。分离后，用 cAMP 和 MPA 重新蜕膜化 DSC，并评估蜕膜化标志物 IGFBP-1 和催乳素的分泌情况。我们使用 EVT 细胞系 SGHPL-4 研究了 DSC 分泌因子对滋养细胞功能的影响。我们证明了暴露于蜕膜因子的 DSC 能够重新蜕膜化，并且在高 RI 妊娠中，DSC 对滋养细胞的趋化作用受损。这项研究提供了关于 DSC 在调节妊娠早期 EVT 功能中的作用的新见解。这是第一项证明在妊娠早期血管重塑受损的妊娠中，DSC 分泌抑制滋养细胞定向运动的因子的研究。这一发现对于理解血管重塑受损的妊娠中异常的滋养细胞侵袭可能很重要。
