Different degrees of vascularization and their relationship to the expression of vascular endothelial growth factor, placental growth factor, angiopoietins, and their receptors in first-trimester decidual tissues

ObjectiveTo evaluate vascular adaptation to implantation by studying vascularization and angiogenic factors in the decidua basalis (DB), decidua parietalis, and decidual secretory endometrium of first-trimester pregnancies. Comparison of these tissues provides information about the regulation of vascularization by pregnancy-induced hormones and/or the extravillous trophoblast (EVT).DesignProspective study.SettingLeids University Medical Center (LUMC).Patient(s)Women (n = 32) undergoing voluntarily first-trimester termination of pregnancy.Intervention(s)Decidual samples from vacuum-aspiration.Main Outcome Measure(s)Evaluation of vascularization, determined by CD34 immunohistochemistry, and vascular endothelial growth factor-A, placental growth factor (PlGF), vascular endothelial growth factor receptor 1 (Flt-1), vascular endothelial growth factor receptor 2, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and TIE-2 protein and messenger RNA (mRNA) expression, determined by reverse transcriptase-polymerase chain reaction and immunohistochemistry, in serial paraffin sections.Result(s)Pregnancy-induced hormones and EVT influence vascularization by enhancing the vascular and luminal surface, and by reducing vessel density at the implantation site. These changes correlate with differences in gene and protein expression. Placental growth factor mRNA and PlGF and Flt-1 protein expressions were elevated in DB under the influence of EVT. In addition, the angiopoietins were differentially expressed, in favor of Ang-2, in DB.Conclusion(s)The EVT and pregnancy-induced hormones might be associated with the regulation of vascularization and the expression of angiogenic factors in decidua. The induction of PlGF and Flt-1, and the Ang-2:Ang-1 ratio in DB, suggest that these factors play a role in regulating angiogenesis at the implantation site.