title: Placental development during early pregnancy in sheep: vascular growth and expression of angiogenic factors in maternal placenta.
abstract: Placental vascular development (angiogenesis) is critical for placental function and thus for normal embryonic/fetal growth and development. Specific environmental factors or use of assisted reproductive techniques may result in poor placental angiogenesis, which may contribute to embryonic losses and/or fetal growth retardation. Uterine tissues were collected on days 14, 16, 18, 20, 22, 24, 26, 28, and 30 after mating and on day 10 after estrus (nonpregnant controls) to determine vascular development and expression of several factors involved in the regulation of angiogenesis in the endometrium. Compared with controls, several measurements of endometrial vascularity increased (P<0.001) including vascular labeling index (LI; proportion of proliferating cells), the tissue area occupied by capillaries, area per capillary (capillary size), total capillary circumference per unit of tissue area, and expression of factor VIII (marker of endothelial cells), but capillary number decreased (P<0.001). Compared with controls, mRNA for placental growth factor, vascular endothelial growth factor receptors, angiopoietins (ANGPT) 1 and 2, ANGPT receptor TEK, endothelial nitric oxide synthase, and hypoxia-inducible factor 1alpha increased (P<0.05) during early pregnancy. Vascular LI was positively correlated (P<0.05) with several measurements of vascularity and with mRNA expression of angiogenic factors. These data indicate that endometrial angiogenesis, manifested by increased vascularity and increased expression of several factors involved in the regulation of angiogenesis, is initiated very early in pregnancy. This more complete description of early placental angiogenesis may provide the foundation for determining whether placental vascular development is altered in compromised pregnancies.
authors.affiliation: Department of Animal Science, Center for Nutrition and Pregnancy, Cell Biology Center, North Dakota State University, Fargo, North Dakota 58105, USA. anna.grazul-bilska@ndsu.edu
authors.forename: Anna T
authors.initials: AT
authors.lastname: Grazul-Bilska
authors.forename: Pawel P
authors.initials: PP
authors.lastname: Borowicz
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Johnson
authors.forename: Megan A
authors.initials: MA
authors.lastname: Minten
authors.forename: Jerzy J
authors.initials: JJ
authors.lastname: Bilski
authors.forename: Robert
authors.initials: R
authors.lastname: Wroblewski
authors.forename: Dale A
authors.initials: DA
authors.lastname: Redmer
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Reynolds
mesh_terms: D000328:Adult; D042501:Angiogenic Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004717:Endometrium / Q000254:growth & development / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D018919:Neovascularization, Physiologic / Q000502:physiology*; D021041:Placental Circulation / Q000502:physiology*; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep / Q000502:physiology*
chemical_list: D042501:Angiogenic Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D005169:Factor VIII