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Hum. Reprod. Advance Access published online on October 14, 2008
Human Reproduction, doi:10.1093/humrep/den296
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Decidual vascularization and the expression of angiogenic growth factors and proteases in first trimester spontaneous abortions

M. Plaisier1,2,4, I. Dennert2, E. Rost2, P. Koolwijk1,3, V.W.M. van Hinsbergh3 and F.M. Helmerhorst2

1 Department Biomedical Research, Gaubius Laboratory TNO-Quality and Life, PB Box 2215, Leiden 2301 CE, The Netherlands 2 Department of Gynaecology and Reproductive Medicine, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands 3 Department of Physiology, Institute for Cardiovascular Research, VU University Medical Centre, van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands

4 Correspondence address. Fax: +31-71-5248181; E-mail: m.plaisier{at}lumc.nl

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.

Key words: decidua/vascularization/angiogenic factors/missed abortion/uterine natural killer cells

Submitted on October 3, 2007; resubmitted on May 15, 2008; accepted on May 22, 2008.


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