Abstract
s / Placenta 34 (2013) A1–A99 A83 P2.79. THROMBIN ACTIVATION OF MATERNAL PLATELETS CAUSES PLACENTAL DEVELOPMENTAL FAILURE THROUGH A MECHANISM INDEPENDENT OF THROMBOSIS IN A MURINE HIGH-RISK PREGNANCY MODEL Vidhyalakshmi Arumugam, Jianzhong An, Michelle Bordas, Rashmi Sood Medical College of Wisconsin, Milwaukee, WI, USA Objectives: Maternal thrombophilia is a risk factor for placenta-mediated pregnancycomplications. Themechanism is suspected to involve thrombotic occlusion of the uteroplacental circulation.We examined the role of platelet aggregation in the mechanism of placental failure in a thrombophilia-associatedmurine high-risk pregnancy model (J. Exp. Med., PMID 17438064).We have shown that treatment with heparin prevents placental failure independent of anticoagulation in this model (Blood, PMID 23325830). Yet, thrombin receptor on maternal platelets mediates placental failure. Methods: Integrin aIIbb3 is essential for stable platelet aggregation following activation by thrombin. Experimental FVQ/QThbdPro/+ females were made deficient in aIIb using breeding strategies. Collagen receptor GPVI was depleted using pharmacological tools. Timed pregnancies with ThbdPro/Pro males were evaluated; 50% ThbdPro/Pro embryos are expected from this cross. P-values were computed using c2 GOF and Fisher's exact test of independence. Results: (Tabulated) Embryos homozygous for a prothromboticmutation in thrombomodulin (ThbdPro/Pro) die in utero from placental developmental failure in pregnancies of mothers homozygous for factor V Leiden polymorphism (FVQ/Q) (row 1, P1⁄40.000003), but survive if the mother lacks thrombin receptor, Par4 (row 2; P1⁄40.003 versus row 1). Absence of aIIbb3 from maternal platelets did not improve survival of ThbdPro/Pro embryos (row 3; P[0.52 versus row 1). Depletion of GPVI slightly improved survival but did not reach statistical significance (row 4, P1⁄40.09 versus row 1). Treatment # live embryos # (%age) aborted
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