Moindjie Hadia, Santos Esther Dos, Loeuillet Laurence, Gronier Héloise, de Mazancourt Philippe, Barnea Eytan R, Vialard François, Dieudonne Marie-Noëlle
UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France.
UPRES-EA 2493, Université de Versailles-St-Quentin, Unité de Formation et de Recherche des Sciences de la Santé-Simone Veil, Montigny-le-Bretonneux, France Service de Biologie Médicale, Centre Hospitalier de Poissy-Saint Germain, Poissy, France.
Biol Reprod. 2014 Nov;91(5):118. doi: 10.1095/biolreprod.114.119156. Epub 2014 Sep 17.
Preimplantation factor (PIF) is a peptide secreted by viable mammalian embryos. Moreover, it can be detected in the circulation of pregnant women. Recently, it was shown that PIF promotes invasion in trophoblast cell lines in vitro. Successful human embryo implantation depends on a deep and highly controlled invasion of extravillous trophoblast (EVT) in the maternal endometrium. Trophoblast invasion is regulated in part by matrix metalloproteinase (MMP) activity and integrin expression. The present study demonstrates the presence of PIF in early pregnancy and characterizes its effects on primary human trophoblast invasion. At the fetomaternal interface, intense PIF labeling by immunohistochemistry was present during early gestation in villous trophoblasts and EVTs. A decrease of labeling was observed at term. Furthermore, PIF significantly promoted invasion of human EVT isolated from first-trimester placenta. The proinvasive regulatory effect of PIF in EVT was associated with 1) increased MMP9 activity and 2) reduced tissue inhibitor of metalloproteinase-1 (TIMP1) mRNA expression. PIF also regulated alpha v and alpha 1 integrin mRNA expressions. Last, the proinvasive effect of PIF appeared to be mediated by the mitogen-activated protein kinase (MAPK), phosphoinositide-3-kinase (PI3K), and Janus-kinase signal transducer and activator of transcription (JAK-STAT) signaling pathways. In summary, this work describes the direct, positive effect of PIF on the control of human trophoblastic cell invasion by modulation of MMP/TIMP balance and integrin expression. Moreover, these results suggest that PIF is involved in pathological pregnancies characterized by insufficient or excessive trophoblast invasion.
着床前因子（PIF）是一种由存活的哺乳动物胚胎分泌的肽。此外，在孕妇的血液循环中也能检测到它。最近有研究表明，PIF在体外可促进滋养层细胞系的侵袭。成功的人类胚胎着床依赖于绒毛外滋养层（EVT）对母体子宫内膜进行深度且高度受控的侵袭。滋养层侵袭部分受基质金属蛋白酶（MMP）活性和整合素表达的调节。本研究证实了妊娠早期PIF的存在，并描述了其对原代人滋养层侵袭的影响。在母胎界面，免疫组织化学显示在妊娠早期绒毛滋养层细胞和EVT中存在强烈的PIF标记。足月时标记减少。此外，PIF显著促进了从孕早期胎盘分离的人EVT的侵袭。PIF对EVT的促侵袭调节作用与以下两点有关：1）MMP9活性增加；2）金属蛋白酶组织抑制剂-1（TIMP1）mRNA表达降低。PIF还调节αv和α1整合素mRNA的表达。最后，PIF的促侵袭作用似乎是由丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶（PI3K）和Janus激酶信号转导子及转录激活子（JAK-STAT）信号通路介导的。总之，这项工作描述了PIF通过调节MMP/TIMP平衡和整合素表达对人类滋养层细胞侵袭控制的直接、积极作用。此外，这些结果表明PIF参与了以滋养层侵袭不足或过度为特征的病理性妊娠。
