title: Fibrinogen stabilizes placental-maternal attachment during embryonic development in the mouse.
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.
authors.affiliation: W. M. Keck Center for Transgene Research, Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwaki
authors.forename: Mayra J
authors.initials: MJ
authors.lastname: Sandoval-Cooper
authors.forename: Melissa
authors.initials: M
authors.lastname: Paiva
authors.forename: Takao
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ploplis
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000347:Afibrinogenemia / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D010064:Embryo Implantation / Q000235:genetics; D005260:Female; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000209:etiology* / Q000378:metabolism
chemical_list: D005340:Fibrinogen