It is well known that placental function has a major impact on fetal growth and development and thus on reproductive efficiency and health. Recent studies, including those in gene-knockout mice, indicate that vascular endothelial growth factors (VEGF), fibroblast growth factors (FGF), and angiopoietins (ANG) play major roles in the development and organization of the placental vasculature. The Long-term Goal of this proposal is to determine the role of these major angiogenic growth factors in placental angiogenesis during normal and compromised pregnancies.
In Specific Aim 1, we will test Hypothesis l: that major angiogenic factors, namely VEGF, basic FGF (bFGF or FGF 2), and -ANG1, and their receptors, are expressed in a time- and cell-specific fashion throughout gestation. In this study, we also will correlate placental vascular development with the pattern of expression of these major angiogenic factors and their receptors in normal pregnancies.
In Specific Aim 2, we will test Hypothesis 2: that placental size is determined by the fetal genome but that placental vascularity depends primarily on the maternal genome (the """"""""uterine environment""""""""); additionally we hypothesize that differences in placental vascularity can be explained by changes in placental expression of VEGF, bFGF, ANG1, and(or) their receptors. For this study, we will use a model that we have recently established for reciprocal embryo transfer between a highly prolific and a less prolific breed of sheep.
In Specific Aims 3 and 4, we will test Hypotheses 3 and 4: that decreased placental and fetal size resulting ' from maternal undernutrition (Specific Aim 3) or maternal age at first pregnancy (Specific Aim 4) can be explained by reduced placental expression of the major angiogenic factors and(or) their receptors resulting in reduced placental vascular development. The proposed studies wilt provide a solid foundation for future studies and, in addition, address important issues in pregnancy research; namely, the effects of the fetal and maternal genomes, maternal undernutrition, and maternal age, respectively, on placental vascular development.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064141-02
Application #
6499046
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Pearson, Gail D
Project Start
2001-02-01
Project End
2005-01-31
Budget Start
2002-02-01
Budget End
2003-01-31
Support Year
2
Fiscal Year
2002
Total Cost
$141,000
Indirect Cost
Name
North Dakota State University
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
City
Fargo
State
ND
Country
United States
Zip Code
58108
Johnson, M L; Redmer, D A; Reynolds, L P et al. (2017) Gap junctional connexin messenger RNA expression in the ovine uterus and placenta: effects of estradiol-17?-treatment, early pregnancy stages, and embryo origin. Domest Anim Endocrinol 58:104-112
Reynolds, L P; Haring, J S; Johnson, M L et al. (2015) Placental development during early pregnancy in sheep: estrogen and progesterone receptor messenger RNA expression in pregnancies derived from in vivo-produced and in vitro-produced embryos. Domest Anim Endocrinol 53:60-9
Grazul-Bilska, Anna T; Johnson, Mary Lynn; Borowicz, Pawel P et al. (2014) Placental development during early pregnancy in sheep: effects of embryo origin on vascularization. Reproduction 147:639-48
Lemley, C O; Meyer, A M; Neville, T L et al. (2014) Dietary selenium and nutritional plane alter specific aspects of maternal endocrine status during pregnancy and lactation. Domest Anim Endocrinol 46:1-11
Meyer, A M; Neville, T L; Reed, J J et al. (2013) Maternal nutritional plane and selenium supply during gestation impact visceral organ mass and intestinal growth and vascularity of neonatal lamb offspring. J Anim Sci 91:2628-39
Grazul-Bilska, Anna T; Borowicz, Pawel P; Reynolds, Lawrence P et al. (2013) Vascular perfusion with fluorescent labeled lectin to study ovarian functions. Acta Histochem 115:893-8
Grazul-Bilska, Anna T; Johnson, Mary Lynn; Borowicz, Pawel P et al. (2013) Placental development during early pregnancy in sheep: effects of embryo origin on fetal and placental growth and global methylation. Theriogenology 79:94-102
Meyer, A M; Reed, J J; Neville, T L et al. (2012) Effects of nutritional plane and selenium supply during gestation on visceral organ mass and indices of intestinal growth and vascularity in primiparous ewes at parturition and during early lactation. J Anim Sci 90:2733-49
Reynolds, Lawrence P; Caton, Joel S (2012) Role of the pre- and post-natal environment in developmental programming of health and productivity. Mol Cell Endocrinol 354:54-9
Meyer, A M; Reed, J J; Neville, T L et al. (2011) Nutritional plane and selenium supply during gestation affect yield and nutrient composition of colostrum and milk in primiparous ewes. J Anim Sci 89:1627-39

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