Placental growth factor (PlGF) as an angiogenic/inflammatory switcher: lesson from early pregnancy losses

Abstract

Placental growth factor (PlGF) is an angiogenic factor which belongs to vascular endothelial growth factor (VEGF) family. In addition to the angiogenic function of PlGF, in some conditions such as preeclampsia and early pregnancy losses, it can induce inflammatory reactions which could be accompanied with reduced angiogenesis. Hence, it is crucial to investigate inflammatory and angiogenic switching states and understand underlying mechanisms. PlGF is expressed in endometrium, placenta and trophoblast cells and is involved in maturation of uterine NK cells. Up-regulation of PlGF directs VEGF to VEGFR-2 and reinforces angiogenesis. However, when VEGF/VEGFR-2 signaling pathway is impaired, PlGF may shift to severe inflammation and cause tissue damages which could lead to early pregnancy losses. Downregulation of PlGF has also been reported in pregnancy complications. In this review, we discussed the role of PlGF in embryo implantation failure and early pregnancy loss and also possible mechanisms regarding the role of PlGF in angiogenic/inflammatory switching in early pregnancy losses. Furthermore, we summarized the effects of various compounds on PlGF expression and briefly talked about its therapeutic potential that may be an opportunity for prevention of pregnancy loss.

Lymphocytes immunotherapy for preserving pregnancy: Mechanisms and Challenges

“…Numerous processes such as immune changes at the fetal-maternal interface and peripheral immune responses are involved in the induction of maternal tolerance, 15 and it has been demonstrated that in some cases of reproductive disturbances, function and/or the number of immune cells are altered. 16,17 Regulatory T (Treg) cells, natural killer (NK) cells, T helper (Th) 1, Th2, Th17, and macrophages are the main immune cells in regulation of maternal tolerance and prevention of fetus rejection. 18,19 During the pre-implantation, premenstrual, menses, and also the early pregnancy, there is a large accumulation of endometrial leukocytes in the endometrium.…”

Anti-placental growth factor antibody ameliorates hyperoxia-mediated impairment of lung development in neonatal rats

“…The pro-inflammatory effects of PGF have been observed in various cells and organs (31)(32)(33). Therefore, the level of inflammatory cytokines can also be measured to verify the function of the anti-PGF antibody.…”

Preeclampsia: a gestational cardiorenal syndrome

“…It is still to be elucidated whether maternal endothelium dysfunction prior to conception is a prerequisite for development of preeclampsia, or whether sometimes this complication results from an imbalanced mother‐conceptus communication during implantation, a process involving numerous cellular, molecular and biochemical mechanisms such as angiogenetic factors (Boeldt & Bird, ; Nejabati et al . ) , cellular exosomes (Burnett & Nowak, ), oxygen tension (Burton, ), leucocytes (Lima et al . ), natural killer (Chen et al .…”

“…Endothelium dysfunction has been reported as a direct consequence of pre-existing cardiac and/or renal dysfunction, clinically illustrated by the generalized endothelial dysfunction in congestive heart failure (Bauersachs & Schäfer, 2004) and in individuals with a congenital reduction in the number of nephrons (Keller et al 2003;Zoccali, 2007). The normal or abnormal function of the maternal endothelium is known to be strongly linked with the process of embryo implantation, where numerous hormones, cytokines, immunomodulatory and vaso-active mechanisms are involved in the adaptation process of the maternal vasculature (Burton 2009;Lima et al 2014;Burnett & Nowak, 2016;Boeldt & Bird, 2017;Chen et al 2017;Nejabati et al 2017;Robertson et al 2018).…”

“…Today, evidence is growing that pre-existing or early pregnancy suboptimal cardiac dysfunction may predispose to subsequent placental maldevelopment (Mahendru et al 2013;Foo et al 2018;Thilaganathan & Kalafat, 2019) and worsening maternal cardiovascular function with the increased volume load of pregnancy (Melchiorre et al 2016;Buddeberg et al 2018a,b). It is still to be elucidated whether maternal endothelium dysfunction prior to conception is a prerequisite for development of preeclampsia, or whether sometimes this complication results from an imbalanced mother-conceptus communication during implantation, a process involving numerous cellular, molecular and biochemical mechanisms such as angiogenetic factors (Boeldt & Bird, 2017;Nejabati et al 2017), cellular exosomes (Burnett & Nowak, 2016), oxygen tension (Burton, 2009), leucocytes (Lima et al 2014), natural killer (Chen et al 2017) and regulatory T cells (Robertson et al 2018). Longitudinal studies from preconception to postpartum, such as reported by Foo et al (2018), are needed to find out whether all women with early-onset preeclampsia had pregestational cardiovascular dysfunction or whether women with normal cardiovascular function can also develop this complication.…”