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(American Journal of Pathology. 2002;160:1021-1034.)
© 2002 American Society for Investigative Pathology

Regular Articles

Fibrinogen Stabilizes Placental-Maternal Attachment During Embryonic Development in the Mouse

From the W. M. Keck Center for Transgene Research and theDepartment of Chemistry and Biochemistry, University of NotreDame, Notre Dame, Indiana

In humans, maternal fibrinogen (Fg) is required to support pregnancies by maintaining hemostatic balance and stabilizing uteroplacental attachment at the fibrinoid layer found at the fetal-maternal junction. To examine relationships between low Fg levels and early fetal loss, a genetic model of afibrinogenemia was developed. Pregnant mice homozygous for a deletion of the Fg- chain, which results in a total Fg deficiency state (FG^-/-), aborted the fetuses at the equivalent gestational stage seen in humans. Results obtained from timed matings of FG^-/- mice showed that vaginal bleeding was initiated as early as embryonic day (E)6 to 7, a critical stage for maternal-fetal vascular development. The condition of afibrinogenemia retarded embryo-placental development, and consistently led to abortion and maternal death at E9.75. Lack of Fg did not alter the extent or distribution pattern of other putative factors of embryo-placental attachment, including laminin, fibronectin, and Factor XIII, indicating that the presence of fibrin(ogen) is required to confer sufficient stability at the placental-decidual interface. The results of these studies demonstrate that maternal Fg plays a critical role in maintenance of pregnancy in mice, both by supporting proper development of fetal-maternal vascular communication and stabilization of embryo implantation.

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