Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions.
BACKGROUND
Decidual vascular development is important for implantation. This study analysed decidual vascular adaptation to implantation in correlation with miscarriage in decidual secretory endometrium (DSE), decidua parietalis (DP) and decidua basalis (DB) of miscarriage patients and matched controls.


METHODS
Decidua was obtained during first trimester termination of pregnancy (controls) and vacuum aspiration in case of missed abortion (cases). Vascularization and the expression of VEGF-A, placental growth factor, Flt-1, KDR, angiopoietin (Ang)-1, Ang-2, TIE-2, and membrane-type matrix metalloproteinases MT1-, MT2-, MT3- and MT5-MMP were determined at mRNA and protein level. Uterine natural killer cells (CD56), macrophages (CD68), proliferation (Ki67) and apoptosis (activated caspase-3) were evaluated in consecutive sections.


RESULTS
Decidual vascularization showed differences between cases and controls, i.e. fewer vessels with larger circumference in cases. This correlated with the differential expressions of various factors at mRNA/antigen level and with increased endothelial flt1, KDR, MT2- and MT5-MMP expression in miscarriage patients. The differences between cases and controls were probably not based on altered proliferation and/or apoptosis, since Ki67 and active Caspase-3 showed comparable expression levels in both groups. Although DB of cases and controls showed similar amounts of CD56- and CD68-positive cells, the case group did show elevated levels of CD56 in DSE (P < 0.05) and of CD68 in DP compared with the control group (P < 0.05).


CONCLUSIONS
The differences in vascularization and in the expression of angiogenic factors and proteases between groups suggest a correlation between decidual vascularization and the occurrence of miscarriages.
Plaisier
M
M
Department Biomedical Research, Gaubius Laboratory TNO-Quality and Life, PB Box 2215, Leiden 2301 CE, The Netherlands. m.plaisier@lumc.nl
Dennert
I
I
Rost
E
E
Koolwijk
P
P
van Hinsbergh
V W M
VW
Helmerhorst
F M
FM
D000022:Abortion, Spontaneous / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D042501:Angiogenic Proteins / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D003656:Decidua / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D010064:Embryo Implantation / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D012333:RNA, Messenger / Q000378:metabolism; D000097382:CD68 Molecule
D042501:Angiogenic Proteins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D019002:CD56 Antigen; D053148:Caspase 3; D019394:Ki-67 Antigen; D010447:Peptide Hydrolases; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C505407:CASP3 protein, human