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Down-regulation of placental neuropilin-1 in fetal growth restriction
- Source :
- American Journal of Obstetrics and Gynecology. 214:279.e1-279.e9
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- BackgroundFetal growth restriction (FGR) is associated with adverse outcomes extending from fetal to adult life, and thus, constitutes a major health care challenge. Fetuses with progressive growth restriction show increasing impedance in the umbilical artery flow, which may become absent during end-diastole. Absent end-diastolic flow (AEDF) is associated with adverse perinatal outcomes including stillbirths and perinatal asphyxia. Placentas from such pregnancies demonstrate deficient fetoplacental vascular branching. Current evidence, moreover, indicates an antiangiogenic state in maternal circulation in several pregnancy complications including preeclampsia, small-for-gestational-age births, fetal death, and preterm labor. The angiogenic mediators in maternal circulation are predominantly of placental origin. Information, however, on the role of specific proangiogenic and antiangiogenic mechanisms operating at the placental level remains limited. Elucidation of these placenta-specific angiogenic mechanisms will not only extend our understanding of the causal pathway for restricted fetal growth but may also lead to the development of biomarkers that may allow early recognition of FGR.ObjectiveWe sought to test the hypothesis that fetoplacental angiogenic gene expression is altered in pregnancies complicated with FGR and umbilical artery Doppler AEDF.Study DesignPlacental samples were collected from FGR pregnancies complicated with umbilical artery Doppler AEDF (study group, n = 7), and from uncomplicated pregnancies (control group, n = 7), all delivered by cesarean during the last trimester of pregnancy. Angiogenic oligonucleotide microarray analysis was performed and was corroborated by quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. The Student t test with Bonferroni correction was used with P < .05 considered statistically significant. Independent groups t test was used to analyze the immunostain intensity scores with a P < .05 considered statistically significant.ResultsOur microarray results showed that among several differentially expressed angiogenic genes in the growth-restricted group, only the down-regulation of neuropilin (NRP)-1 was most significant (P < .0007). Quantitative real-time polymerase chain reaction confirmed a significantly lower NRP-1 gene expression in the FGR group than in the control group (mean ± SD ˆcycle threshold: 0.624 ± 0.55 and 1.325 ± 0.84, respectively, P = .04). Western blot validated significantly lower NRP-1 protein expression in the FGR group than in the control group (mean ± SD NRP-1/β-actin ratio: 0.13 ± 0.04 and 0.34 ± 0.05, respectively, P < .001). Finally, immunohistochemistry of placental villi further corroborated a significantly decreased expression of NRP-1 in the FGR group (P = .006).ConclusionThe study demonstrated significant down-regulation of placental NRP-1 expression in FGR pregnancies complicated with AEDF in umbilical artery. As NRP-1 is known to promote sprouting angiogenesis, its down-regulation may be involved in the deficient vascular branching observed in FGR placentas suggesting the presence of an antiangiogenic state. Further studies may elucidate such a causal role and may lead to the development of novel diagnostic and therapeutic tools.
- Subjects :
- 0301 basic medicine
Placenta
real-time polymerase chain reaction
Umbilical Arteries
Cohort Studies
fetal growth restriction
small for gestational age
0302 clinical medicine
Diastole
Pregnancy
Obstetrics and Gynaecology
Neuropilin 1
Prospective Studies
microarrays
Oligonucleotide Array Sequence Analysis
Fetal Growth Retardation
030219 obstetrics & reproductive medicine
Reverse Transcriptase Polymerase Chain Reaction
Obstetrics and Gynecology
medicine.anatomical_structure
Infant, Small for Gestational Age
immunohistochemistry
Female
Adult
medicine.medical_specialty
umbilical artery absent end-diastolic flow
Blotting, Western
Down-Regulation
Neovascularization, Physiologic
Ultrasonography, Prenatal
Preeclampsia
Young Adult
03 medical and health sciences
medicine.artery
Internal medicine
medicine
Humans
Placental Circulation
RNA, Messenger
Sprouting angiogenesis
antiangiogenic state
Fetus
business.industry
Gene Expression Profiling
Infant, Newborn
Ultrasonography, Doppler
Umbilical artery
medicine.disease
placental branching angiogenesis
neuropilin-1
030104 developmental biology
Endocrinology
Gene Expression Regulation
Case-Control Studies
business
Subjects
Details
- ISSN :
- 00029378
- Volume :
- 214
- Database :
- OpenAIRE
- Journal :
- American Journal of Obstetrics and Gynecology
- Accession number :
- edsair.doi.dedup.....8ea0777fa20751dca8c5de2f3f320f6d