Document Detail

Survival and size are differentially regulated by placental and fetal PKBalpha/AKT1 in mice.
MedLine Citation:
PMID:  20980686     Owner:  NLM     Status:  MEDLINE    
The importance of placental circulation is exemplified by the correlation of placental size and blood flow with fetal weight and survival during normal and compromised human pregnancies in such conditions as preeclampsia and intrauterine growth restriction (IUGR). Using noninvasive magnetic resonance imaging, we evaluated the role of PKBalpha/AKT1, a major mediator of angiogenesis, on placental vascular function. PKBalpha/AKT1 deficiency reduced maternal blood volume fraction without affecting the integrity of the fetomaternal blood barrier. In addition to angiogenesis, PKBalpha/AKT1 regulates additional processes related to survival and growth. In accordance with reports in adult mice, we demonstrated a role for PKBalpha/AKT1 in regulating chondrocyte organization in fetal long bones. Using tetraploid complementation experiments with PKBalpha/AKT1-expressing placentas, we found that although placental PKBalpha/AKT1 restored fetal survival, fetal PKBalpha/AKT1 regulated fetal size, because tetraploid complementation did not prevent intrauterine growth retardation. Histological examination of rescued fetuses showed reduced liver blood vessel and renal glomeruli capillary density in PKBalpha/Akt1 null fetuses, both of which were restored by tetraploid complementation. However, bone development was still impaired in tetraploid-rescued PKBalpha/Akt1 null fetuses. Although PKBalpha/AKT1-expressing placentas restored chondrocyte cell number in the hypertrophic layer of humeri, fetal PKBalpha/AKT1 was found to be necessary for chondrocyte columnar organization. Remarkably, a dose-dependent phenotype was exhibited for PKBalpha/AKT1 when examining PKBalpha/Akt1 heterozygous fetuses as well as those complemented by tetraploid placentas. The differential role of PKBalpha/AKT1 on mouse fetal survival and growth may shed light on its roles in human IUGR.
Vicki Plaks; Elina Berkovitz; Katrien Vandoorne; Tamara Berkutzki; Golda M Damari; Rebecca Haffner; Nava Dekel; Brian A Hemmings; Michal Neeman; Alon Harmelin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-27
Journal Detail:
Title:  Biology of reproduction     Volume:  84     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-23     Completed Date:  2011-06-14     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  537-45     Citation Subset:  IM    
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MeSH Terms
Body Size / genetics*
Embryo, Mammalian
Fetal Growth Retardation / genetics,  metabolism,  pathology
Fetal Viability / genetics*,  physiology
Fetus / metabolism,  physiology*
Gestational Age
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Placenta / metabolism*
Proto-Oncogene Proteins c-akt / genetics,  metabolism,  physiology*
Grant Support
232640//European Research Council
Reg. No./Substance:
EC protein, mouse; EC Proteins c-akt

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