Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-2530
Gassmann, M; Manini, A; Stallmach, T; Saam, B; Kuhn, Gi; Grenacher, B; Bogdanova, A Y; Vogel, J (2008). Abortion in mice with excessive erythrocytosis is due to impaired arteriogenesis of the uterine arcade. Biology of Reproduction, 78(6):1049-57.
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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Veterinary Physiology|
04 Faculty of Medicine > Center for Integrative Human Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||06 Jun 2008 13:44|
|Last Modified:||27 Nov 2013 17:44|
|Publisher:||Society for the Study of Reproduction|
|Citations:||Web of Science®. Times cited: 5|
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