Fibrinogen stabilizes placental-maternal attachment during embryonic development in the mouse

Am J Pathol. 2002 Mar;160(3):1021-34. doi: 10.1016/S0002-9440(10)64923-1.

Abstract

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-gamma 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abortion, Spontaneous / etiology*
  • Abortion, Spontaneous / genetics
  • Abortion, Spontaneous / metabolism
  • Afibrinogenemia / complications*
  • Afibrinogenemia / genetics
  • Afibrinogenemia / metabolism
  • Animals
  • Embryo Implantation* / genetics
  • Female
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Maternal-Fetal Exchange* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Placenta / metabolism*
  • Placenta / pathology
  • Pregnancy
  • Pregnancy Complications, Hematologic / etiology*
  • Pregnancy Complications, Hematologic / metabolism

Substances

  • Fibrinogen