Gayatri Ravikumar1, Arpita Mukhopadhyay2, Ceera Mani2, Prachi Kocchar2, Julian Crasta1, Tinku Thomas3, Pratibha Dwarkanath2, Annamma Thomas4, Anura V Kurpad5, Tirumalai Srinivas Sridhar6. 1. a Department of Pathology, St. John's Medical College , St. John's National Academy of Health Sciences , Bangalore , India. 2. b Division of Nutrition, St. John's Research Institute , St. John's National Academy of Health Sciences , Bangalore , India. 3. c Department of Biostatistics, St. John's Medical College , St. John's National Academy of Health Sciences , Bangalore , India. 4. d Department of Obstetrics and Gynaecology, St. John's Medical College Hospital , St. John's National Academy of Health Sciences , Bangalore , India. 5. e Department of Physiology, Division of Nutrition, St. John's Medical College , St. John's National Academy of Health Sciences , Bangalore , India. 6. f Division of Molecular Medicine, St. John's Research Institute , St. John's National Academy of Health Sciences , Bangalore , India.
Abstract
OBJECTIVES: Aberrations in placental vascular development compromising fetal supply of oxygen and essential nutrients can be a significant contributor to intrauterine growth restriction (IUGR). The development of placental vascular tree is under the influence of two families of growth factors, namely the vascular endothelial growth factor (VEGF) family and angiopoietin/TEK family. In this study, we have examined the expression of angiogenesis-related growth factors, mainly VEGF family and angiopoietin-TEK (endothelial-specific receptor tyrosine kinase) family genes in placentae from IUGR pregnancies uncomplicated by preeclampsia (PE) compared to normal pregnancies. METHODS: Placentae from normotensive IUGR (n = 42) and appropriate for gestational age (AGA) pregnancies (n = 47) were collected and examined histologically. Clinical parameters were obtained from the medical records. Real-time quantitative PCR was performed to assess placental transcript abundance of VEGF, PGF, FLT1, ANGPT1, ANGPT2, and TEK normalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal, placental, and neonatal parameters were tested. RESULTS: Placental transcript abundance for VEGF (relative expression 10.81 versus 12.98, p < .001), PGF (12.14 versus 13.8, p < .001) and ANGPT2 (3.67 versus 9.55, p = .002) were significantly lower in IUGR placentae compared to AGA. The transcript level of VEGF showed significant negative correlation with birth weight (r = -0.419, p = .006), placental weight (r = -0.318, p = .040), placental length (r = -0.389, p = .011) and breadth (r = -0.308, p = .047) only in the IUGR group. Presence of histopathological features of hypoxia correlated with significantly higher transcript levels of PGF in IUGR placentae (12.6 versus 10.9, p = .046). CONCLUSION: The low levels of VEGF transcripts may be responsible for the impaired angiogenesis in IUGR placentae. The significance of higher relative expression of PGF in the presence of chronic hypoxia needs to be explored.
OBJECTIVES: Aberrations in placental vascular development compromising fetal supply of oxygen and essential nutrients can be a significant contributor to intrauterine growth restriction (IUGR). The development of placental vascular tree is under the influence of two families of growth factors, namely the vascular endothelial growth factor (VEGF) family and angiopoietin/TEK family. In this study, we have examined the expression of angiogenesis-related growth factors, mainly VEGF family and angiopoietin-TEK (endothelial-specific receptor tyrosine kinase) family genes in placentae from IUGR pregnancies uncomplicated by preeclampsia (PE) compared to normal pregnancies. METHODS: Placentae from normotensive IUGR (n = 42) and appropriate for gestational age (AGA) pregnancies (n = 47) were collected and examined histologically. Clinical parameters were obtained from the medical records. Real-time quantitative PCR was performed to assess placental transcript abundance of VEGF, PGF, FLT1, ANGPT1, ANGPT2, and TEK normalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal, placental, and neonatal parameters were tested. RESULTS: Placental transcript abundance for VEGF (relative expression 10.81 versus 12.98, p < .001), PGF (12.14 versus 13.8, p < .001) and ANGPT2 (3.67 versus 9.55, p = .002) were significantly lower in IUGR placentae compared to AGA. The transcript level of VEGF showed significant negative correlation with birth weight (r = -0.419, p = .006), placental weight (r = -0.318, p = .040), placental length (r = -0.389, p = .011) and breadth (r = -0.308, p = .047) only in the IUGR group. Presence of histopathological features of hypoxia correlated with significantly higher transcript levels of PGF in IUGR placentae (12.6 versus 10.9, p = .046). CONCLUSION: The low levels of VEGF transcripts may be responsible for the impaired angiogenesis in IUGR placentae. The significance of higher relative expression of PGF in the presence of chronic hypoxia needs to be explored.
Entities:
Keywords:
ANGPT-2; Angiogenesis; IUGR; VEGF; related genes