In the developed world, the U.S. has the highest rate of adolescent pregnancy, which is associated with increased risk of fetal growth restriction and premature delivery. Both preterm delivery and low birth weight are associated with a much greater risk of neonatal mortality and morbidity, and, in addition, the resulting offspring may be 'programmed' to develop cardiovascular or other significant diseases later in life. While poor socio-economic status and gynecological immaturity are undoubtedly major factors predisposing adolescents to poor pregnancy outcome, maternal growth and nutritional status during pregnancy also play major roles in pregnancy outcome. The proposed studies will use well-defined animal models to examine the impacts of being overfed or underfed, and the role of altered sex steroid levels, on fetal and placental growth and placental vascular development in an ovine model of adolescent pregnancy.
Specific Aim 1 will test Hypothesis 1: that reduced fetal growth due to overnutrition of growing adolescents results from reduced placental vascular development and abnormal expression of placental angiogenic factors;
Specific Aim 2 will test Hypothesis 2: that undernutrition of growing adolescents also reduces fetal growth via altered placental growth and vascular development or, alternatively, by limiting nutrient availability in the maternal circulation;
and Specific Aim 3 will test Hypothesis 3: that reduced fetal and placental growth and vascular development in adolescents due to under- or overnutrition results from altered production or metabolism of sex steroids and, therefore, can be overcome by steroid replacement.
Specific Aim 4 will test Hypothesis 4: that placental angiogenic factor expression can be manipulated in placental tissue explants cultured in vitro using a range of specific hormone and metabolic treatments that replicate elements of those conditions observed in nutritionally compromised pregnancies in vivo. The proposed studies will provide a mechanistic understanding, at the whole animal, organ, and tissue levels, of the factors contributing to altered placental angiogenesis and angiogenic factor expression in the nutritionally compromised adolescent, and thus will provide a powerful basis for future mechanistic studies at the cellular level, while at the same time contributing to the development of informed nutritional strategies to optimize pregnancy outcome in adolescents.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD045784-03
Application #
7218037
Study Section
Special Emphasis Panel (ZRG1-EMNR-A (02))
Program Officer
Grave, Gilman D
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
3
Fiscal Year
2007
Total Cost
$289,432
Indirect Cost
Name
North Dakota State University
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
803882299
City
Fargo
State
ND
Country
United States
Zip Code
58108
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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
Hafez, Shireen A; Borowicz, Pawel; Reynolds, Lawrence P et al. (2010) Maternal and fetal microvasculature in sheep placenta at several stages of gestation. J Anat 216:292-300
Luther, Justin; Aitken, Raymond; Milne, John et al. (2010) Liver iron status and associated haematological parameters in relation to fetal growth and pregnancy outcome in rapidly growing adolescent sheep carrying a singleton lamb derived by embryo transfer. Reprod Fertil Dev 22:1230-6
Redmer, Dale A; Luther, Justin S; Milne, John S et al. (2009) Fetoplacental growth and vascular development in overnourished adolescent sheep at day 50, 90 and 130 of gestation. Reproduction 137:749-57
Wallace, J M; Luther, J S; Milne, J S et al. (2006) Nutritional modulation of adolescent pregnancy outcome -- a review. Placenta 27 Suppl A:S61-8