Leukemia Inhibitory Factor (LIF) Inhibition during Mid-Gestation Impairs Trophoblast Invasion and Spiral Artery Remodelling during Pregnancy in Mice
نویسندگان
چکیده
The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Trophoblast cell proliferation, migration and invasion into the endometrium are fundamental events in the initiation of placentation. Leukemia inhibitory factor (LIF) has been shown to promote trophoblast invasion in vitro, however its precise role in trophoblast invasion in vivo is unknown. We hypothesized that LIF would be required for normal trophoblast invasion and spiral artery remodeling in mice. Both LIF and its receptor (LIFRα) co-localized with cytokeratin-positive invasive endovascular extravillous trophoblasts (EVT) in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via administration of our unique LIFRα antagonist, PEGLA, resulted in abnormal trophoblast invasion and impaired spiral artery remodeling compared to PEG control. PEGLA-treated mouse decidual vessels were characterized by retention of α-smooth muscle actin (αSMA)-positive vascular smooth muscle cells (VSMCs), while PEG control decidual vessels were remodelled by cytokeratin-positive trophoblasts. LIF blockade did not alter F4/80-positive decidual macrophage numbers between treatment groups, but resulted in down-regulation of decidual transcript levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10), which are important immune cell activation factors that promote spiral artery remodeling during pregnancy. Our data suggest that LIF plays an important role in trophoblast invasion in vivo and may facilitate trophoblast-decidual-immune cell cross talk to enable adequate spiral artery remodeling.
منابع مشابه
Blocking Endogenous Leukemia Inhibitory Factor During Placental Development in Mice Leads to Abnormal Placentation and Pregnancy Loss
The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Specialized trophoblast cells derived from the embryonic trophectoderm play a pivotal role in the establishment of the placenta. Leukemia inhibitory factor (LIF) is one of the predominant cytokines present in the placenta during early pregnancy. LIF has been ...
متن کاملI-6: Remodelling Uterine Spiral Arteries inPregnancy
Background: During the first trimester of pregnancy the uterine spiral arteries that supply blood to the placenta are remodelled, creating heavily dilated conduits lacking maternal vasomotor control. To effect permanent vasodilatation, the internal elastic lamina and medial elastic fibres must be degraded. Failure of remodelling is a key characteristic of the pathological placenta and is though...
متن کاملEffect of different concentrations of leukemia inhibitory factor on gene expression of vascular endothelial growth factor-A in trophoblast Tumor Cell Line
Background: Several studies have shown that leukemia inhibitory factor (LIF) is one of the most important cytokinesparticipating in the process of embryo implantation and pregnancy, while, the role of this factor on vascular endothelialfactor-A (VEGF-A), as one of the most important angiogenic factor, has not been fully investigated yet. The aimof this study was to evaluate th...
متن کاملBeyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy
In the first trimester the extravillous cytotrophoblast cells occlude the uterine spiral arterioles creating a low oxygen environment early in pregnancy, which is essential for pregnancy success. Paradoxically, shallow trophoblast invasion and defective vascular remodelling of the uterine spiral arteries in the first trimester may result in impaired placental perfusion and chronic placental isc...
متن کاملP-194: Investigation The Association of Leukemia Inhibitory Factor Gene Polymorphism with IVF Outcome in Infertile Women
Background: Clinical infertility is defined as the inability to become pregnant after 12 months of unprotected intercourse. Worldwide, more than 80 million couples suffer from infertility;the majority of this population are residents of developing countries. In vitro fertilization (IVF) is the most successful of the infertility treatments, and for many people is the last possibility for pregnan...
متن کامل