Physiological and pathological angiogenesis in endometrium at the time of embryo implantation

Abstract

Embryo establishes contact with the endometrium during implantation. Proper endometrial vascular development and maintenance at the time of embryo implantation is crucial for successful pregnancy. Vascular development at the maternal-embryo interface can be regulated by various cell types, of which uterine natural killer (uNK) cells play an important role. Abnormal angiogenesis and uNK cell number/function may lead to reproductive failure, particularly in women with recurrent miscarriage (RM) and women with recurrent implantation failure (RIF) after IVF-ET treatment, which are the important clinical hurdles in reproductive medicine to overcome. In this review, we aim to discuss the current knowledge of physiological angiogenic processes and the pathological angiogenesis at the time of implantation, as well as the possible mechanism and potential treatment.

Porphyromonas gingivalisand adverse pregnancy outcome

“…Taken together, this suggests that A7436, by itself, is unlikely to trigger the overt inflammatory responses that initiate spontaneous preterm labor [15]. Instead, the pathologic features observed with A7436 are more in line with implantation failure or poor placentation, which often occur with recurrent miscarriage, fetal growth restriction, or preeclampsia [14,75,104,105].…”

Preeclampsia: a gestational cardiorenal syndrome

“…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.…”

Intrauterine infusion of human chorionic gonadotropin before embryo transfer in IVF/ET cycle: The critical review

“…Moreover, decay-accelerating factor (DAF), one of complement regulatory proteins to protect host cells from the attack by the activated complement system, was increased in the luminal compartment, potentially to maintain a safe environment for embryonic implantation. 65,68 However, there is still no clinical trial about medical intervention for women with lower uNK counts. Recently, high dose (10 000 IU) of urine-purified hCG was shown to modulate uterine natural killer (uNK) cell proliferation via mannose receptors (CD206), rather than by the classical LH/hCG receptors which are not expressed on uNK cells.…”

“…68 Additional functions of decidual NK cells include trophoblast invasion, spiral artery transformation and decidual differentiation. 68 Additional functions of decidual NK cells include trophoblast invasion, spiral artery transformation and decidual differentiation.…”