Document Detail

Abortion in mice with excessive erythrocytosis is due to impaired arteriogenesis of the uterine arcade.
MedLine Citation:
PMID:  18256329     Owner:  NLM     Status:  MEDLINE    
We postulate that repeated pregnancy loss, intrauterine growth restriction, and preeclampsia are caused by impaired elevation of uterine blood flow due to disturbed arteriogenesis of the uterine arcade. This hypothesis is based on the observation that pregnant human erythropoietin-overexpressing (plasma levels elevated 12-fold) mice (termed tg6 mice) suffering from excessive erythrocytosis generally abort at midgestation unless their hematocrit of 0.85 is drastically lowered. Transgenic mice show placental malformations that parallel those observed in pregnant women suffering from impaired uterine perfusion. Shear stress, a key factor inducing arteriogenesis, was 5-fold lower in tg6 mice compared with wildtype (WT) littermates. Consequently, uterine artery growth was reduced, and dramatically fewer viable pups (1.63 +/- 2.20 vs. 8.10 +/- 0.74 in WT) of lower weight (1.29 +/- 0.07 g vs. 1.62 +/- 0.12 g in WT) were delivered in first pregnancies. Only in subsequent pregnancies did tg6 deliver approximately the expected number of pups. Birth weights of tg6 offspring, however, remained reduced. As the spleen is a major site of extramedullary erythropoiesis in tg6 animals, splenectomy reduced the hematocrit to 0.6-0.7. In turn, shear stress increased to normal values, and splenectomized primiparous tg6 showed normal uterine artery growth and delivery of pups similar in number and weight compared with WT. We conclude that poor arteriogenesis is a previously unappreciated cause for clinically important pregnancy complications.
Max Gassmann; Annamaria Manini; Thomas Stallmach; Bianca Saam; Gisela Kuhn; Beat Grenacher; Anna Y Bogdanova; Johannes Vogel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-02-06
Journal Detail:
Title:  Biology of reproduction     Volume:  78     ISSN:  0006-3363     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-22     Completed Date:  2008-08-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1049-57     Citation Subset:  IM    
Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland.
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MeSH Terms
Abortion, Spontaneous / blood,  etiology*,  genetics,  physiopathology
Arteries / growth & development
Blood Flow Velocity
Blood Viscosity
Erythropoietin, Recombinant / genetics
Infertility, Female / blood,  etiology,  genetics
Mice, Inbred C57BL
Mice, Transgenic
Polycythemia / complications*,  genetics
Uterus / blood supply*
Reg. No./Substance:
0/Erythropoietin, Recombinant

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