Survival and Size Are Differentially Regulated by Placental and Fetal PKBalpha/AKT1 in Mice1
Autor: | Vicki Plaks, Golda M. Damari, Michal Neeman, Brian A. Hemmings, Katrien Vandoorne, Alon Harmelin, Nava Dekel, Tamara Berkutzki, Rebecca Haffner, Elina Berkovitz |
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Rok vydání: | 2011 |
Předmět: |
0303 health sciences
medicine.medical_specialty Fetus Tetraploid complementation assay Placental Circulation Intrauterine growth restriction Cell Biology General Medicine Biology medicine.disease Chondrocyte 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Endocrinology Reproductive Medicine Fetal membrane Placenta Internal medicine embryonic structures medicine 030217 neurology & neurosurgery 030304 developmental biology Blood vessel |
Zdroj: | Biology of Reproduction. 84:537-545 |
ISSN: | 1529-7268 0006-3363 |
Popis: | 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. |
Databáze: | OpenAIRE |
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