| Effects of Reduced Gcm1 Expression on Trophoblast Morphology, Fetoplacental Vascularity, and Pregnancy Outcomes in Mice. | |
| | |
MedLine Citation:
|
PMID: 22275534 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Preeclampsia is a life-threatening disorder characterized by maternal gestational hypertension and proteinuria that results from placental dysfunction. Placental abnormalities include abnormal syncytiotrophoblast and a 50% reduction in placental expression of the transcription factor Gcm1. In mice, homozygous deletion of Gcm1 prevents syncytiotrophoblast differentiation and is embryonic lethal. We used heterozygous Gcm1 mutants (Gcm1(+/-)) to test the hypothesis that hypomorphic expression of placental Gcm1 causes defective syncytiotrophoblast differentiation and maternal and placental phenotypes that resemble preeclampsia. We mated wild-type female mice with Gcm1(+/-) fathers to obtain wild-type mothers carrying ≈50% Gcm1(+/-) conceptuses. Gcm1(+/-) placentas had syncytiotrophoblast abnormalities including reduced gene expression of Gcm1-regulated SynB, elevated expression of sFlt1, a thickened interhemal membrane separating maternal and fetal circulations, and electron microscopic evidence in syncytiotrophoblast of necrosis and impaired maternal-fetal transfer. Fetoplacental vascularity was quantified by histomorphometry and microcomputed tomography imaging. In Gcm1(+/-), it was ≈30% greater than wild-type littermates, whereas placental vascular endothelial growth factor A (Vegfa) expression and fetal and placental weights did not differ. Wild-type mothers carrying Gcm1(+/-) conceptuses developed late gestational hypertension (118±2 versus 109.6±0.7 mm Hg in controls; P<0.05). We next correlated fetoplacental vascularity with placental Gcm1 expression in human control and pathological pregnancies and found that, as in mice, fetoplacental vascularity increased when GCM1 protein expression decreased (R(2)=-0.45; P<0.05). These results support a role for reduced placental Gcm1 expression as a causative factor in defective syncytiotrophoblast differentiation and maternal and placental phenotypes in preeclampsia in humans. |
| | |
Authors:
|
Shannon A Bainbridge; Abhijeet Minhas; Kathie J Whiteley; Dawei Qu; John G Sled; John C P Kingdom; S Lee Adamson |
Related Documents
:
|
3628824 - Affect and nurturance: mechanisms mediating maternal behavior in two female mammals. 22623924 - Micrornas and fetal brain development: implications for ethanol teratology during the s... 10799394 - Physiology of pregnancy and nutrient metabolism. 10683054 - Outcome at age 4 years in offspring of women with maternal phenylketonuria: the materna... 22322134 - Severe pregnancy complications are associated with elevated factor viii plasma activity. 3101734 - Nutritional management of pregnancy in patients on home parenteral nutrition. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-23 |
Journal Detail:
|
Title: Hypertension Volume: - ISSN: 1524-4563 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-25 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7906255 Medline TA: Hypertension Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Departments of Obstetrics and Gynaecology, Physiology, and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Mouse Imaging Centre, Toronto Centre for Phenogenomics, Hospital for Sick Children, Toronto, Ontario, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: High Dietary Salt and Angiotensin II Chronically Increase Renal Sympathetic Nerve Activity: A Direct...
Next Document: Effects of Estrogen on Cardiovascular Injury in Ovariectomized Female DahlS.Z-Leprfa/Leprfa Rats as ...