Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

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.

[img]
Preview
Accepted Version
PDF
1MB

View at publisher

Abstract

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.

Citations

6 citations in Web of Science®
6 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

70 downloads since deposited on 06 Jun 2008
21 downloads since 12 months

Detailed statistics

Additional indexing

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
Language:English
Date:2008
Deposited On:06 Jun 2008 11:44
Last Modified:27 Nov 2013 16:44
Publisher:Society for the Study of Reproduction
ISSN:0006-3363
Publisher DOI:10.1095/biolreprod.107.065532
PubMed ID:18256329

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page