Factor XIII A subunit-deficient mice developed severe uterine bleeding events and subsequent spontaneous miscarriages.
To understand the molecular pathology of factor XIII (FXIII) deficiency in vivo, its A subunit (FXIIIA)-knockout (KO) mice were functionally analyzed. Although homozygous FXIIIA female KO mice were capable of becoming pregnant, most of them died due to excessive vaginal bleeding during gestation. Abdominal incisions revealed that the uteri of the dead mice were filled with blood and that some embryos were much smaller than others within a single uterus. A series of histologic examinations of the pregnant animals suggested that massive placental hemorrhage and subsequent necrosis developed in the uteri of the FXIIIA KO mice on day 10 of gestation. This was true regardless of the genotypes of fetuses. These results are reminiscent of spontaneous miscarriage in pregnant humans with FXIII deficiency and indicate that maternal FXIII plays a critical role in uterine hemostasis and maintenance of the placenta during gestation.
Koseki-Kuno
Shiori
S
Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Iida-Nishi 2-2-2, Yamagata 990-9585 Japan. aichinos@med.id.yamagata-u.ac.jp
Yamakawa
Mitsunori
M
Dickneite
Gerhard
G
Ichinose
Akitada
A
D000034:Abortion, Veterinary / Q000209:etiology*; D000818:Animals; D005177:Factor XIII Deficiency / Q000150:complications* / Q000235:genetics; D026122:Factor XIIIa / Q000235:genetics / Q000502:physiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology; D006470:Hemorrhage / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D010920:Placenta / Q000473:pathology; D010922:Placenta Diseases / Q000209:etiology*; D011247:Pregnancy / Q000502:physiology*; D011250:Pregnancy Complications, Hematologic / Q000209:etiology*; D014592:Uterine Hemorrhage / Q000209:etiology*
D026122:Factor XIIIa