Epithelial membrane protein 2 (EMP2) deficiency alters placental angiogenesis, mimicking features of human placental insufficiency

Autor: Williams, Carmen J, Chu, Alison, Jefferson, Wendy N, Casero, David, Sudhakar, Deepthi, Khurana, Nevil, Hogue, Claire P, Aryasomayajula, Chinmayi, Patel, Priya, Sullivan, Peggy, Padilla-Banks, Elizabeth, Mohandessi, Shabnam, Janzen, Carla, Wadehra, Madhuri
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
placenta
1.1 Normal biological development and functioning
Placenta
Clinical Sciences
homologous recombination
Reproductive health and childbirth
Inbred C57BL
alpha Subunit
Article
angiogenesis
Gene Knockout Techniques
Mice
IUGR
Underpinning research
Pregnancy
Pathology
2.1 Biological and endogenous factors
Animals
Humans
Aetiology
Homologous Recombination
Neovascularization
reproductive and urinary physiology
Pathologic
Pediatric
EMP2
Fibrin
Fetal Growth Retardation
Membrane Glycoproteins
Neovascularization
Pathologic
Animal
Contraception/Reproduction
Uterus
Perinatal Period - Conditions Originating in Perinatal Period
Hypoxia-Inducible Factor 1
alpha Subunit
Placental Insufficiency
Placentation
Trophoblasts
Mice
Inbred C57BL
Oxygen
Disease Models
Animal
Disease Models
embryonic structures
Female
Hypoxia-Inducible Factor 1
Zdroj: The Journal of pathology, vol 242, iss 2
Popis: Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2-/- ) were generated. Emp2-/- females are fertile but have reduced litter sizes when carrying Emp2-/- but not Emp2+/- fetuses. Placentas of Emp2-/- fetuses exhibit dysregulation in pathways related to neoangiogenesis, coagulation, and oxidative stress, and have increased fibrin deposition and altered vasculature. Given that these findings often occur due to placental insufficiency resulting in an oxygen-poor environment, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) was examined. Placentas from Emp2-/- fetuses had increased total HIF-1α expression in large part through an increase in uterine NK (uNK) cells, demonstrating a unique interplay between uNK cells and trophoblasts modulated through EMP2. To determine if these results translated to human pregnancy, placentas from normal, term deliveries or those complicated by placental insufficiency resulting in intrauterine growth restriction (IUGR) were stained for EMP2. EMP2 was significantly reduced in both villous and extravillous trophoblast populations in IUGR placentas. Experiments in vitro using human trophoblast cells lines indicate that EMP2 modulates angiogenesis by altering HIF-1α expression. Our results reveal a novel role for EMP2 in regulating trophoblast function and vascular development in mice and humans, and suggest that it may be a new biomarker for placental insufficiency. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Databáze: OpenAIRE
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