The objective of the Specialized Cooperative Centers Program in Reproduction Research (SCCPRR) at the University of Maryland School of Medicine is to conduct innovative basic and clinical research on female and male reproductive biology and to apply the knowledge gained from these studies to improve understanding of the etiology and treatment of reproductive dysfunction and infertility in women and men. The thematic focus of this proposal is the role that estrogen plays in regulating maturation of primate fetal ovaries and testes during intrauterine development and vascular remodeling of the uterine endometrium during the menstrual cycle. In Project I (Gerald J. Pepe), the regulatory role of estrogen in utero in programming fetal ovarian follicular and oocyte development and the impact this has on fertility in adulthood will be assessed in the baboon. In Project II (Eugene D. Albrecht), the regulatory role of estrogen in utero in programming baboon fetal testicular and excurrent ductule/epididymal development and the impact this has on fertility in adulthood will be assessed. A combined clinical-basic research study is proposed in Project III (Robert D. Koos), to determine the role of estrogen and progesterone, acting via expression of angiostimulatory and angioinhibitory factors, on endometrial angiogenesis and vascular remodeling in vivo in baboons and in vitro in cocultures of human endometrial and vascular endothelial and mural cells. We will collaborate with experts in human and nonhuman primate reproductive biology at the University of Maryland SCCPRR, Eastern Virginia Medical School, the University of Pittsburgh SCCPRR, and the Johns Hopkins University SCCPRR. Each of the research projects will draw heavily upon the immunocytochemistry Core (Gloria E. Hoffman) for the cellular localization/expression of regulatory factors and receptors. Integration of the scientific effort in this SCCPRR will be achieved through the thematic focus on estrogen's role in developmental maturation of the reproductive system, use of the baboon as a nonhuman primate model, and an established tradition of collaborative research. The discoveries obtained in the baboon primate model are expected to translate to the human to advance knowledge of human reproductive biology. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD036207-07
Application #
6888077
Study Section
Special Emphasis Panel (ZHD1-DRG-D (29))
Program Officer
Rankin, Tracy L
Project Start
1998-04-01
Project End
2009-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
7
Fiscal Year
2005
Total Cost
$1,266,896
Indirect Cost
Name
University of Maryland Baltimore
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Pepe, Gerald J; Lynch, Terrie J; Albrecht, Eugene D (2013) Regulation of baboon fetal ovarian development by placental estrogen: onset of puberty is delayed in offspring deprived of estrogen in utero. Biol Reprod 89:132
Bonagura, Thomas W; Zhou, Hui; Babischkin, Jeffery S et al. (2011) Expression of P-450 aromatase, estrogen receptor ? and ?, and ?-inhibin in the fetal baboon testis after estrogen suppression during the second half of gestation. Endocrine 39:75-82
Bonagura, Thomas W; Aberdeen, Graham W; Babischkin, Jeffery S et al. (2010) Divergent regulation of angiopoietin-1 and -2, Tie-2, and thrombospondin-1 expression by estrogen in the baboon endometrium. Mol Reprod Dev 77:430-8
Entezam, Ali; Lokanga, Adihe Rachel; Le, Wei et al. (2010) Potassium bromate, a potent DNA oxidizing agent, exacerbates germline repeat expansion in a fragile X premutation mouse model. Hum Mutat 31:611-6
Albrecht, Eugene D; Pepe, Gerald J (2010) Estrogen regulation of placental angiogenesis and fetal ovarian development during primate pregnancy. Int J Dev Biol 54:397-408
Molitoris, Kristin Happ; Kazi, Armina A; Koos, Robert D (2009) Inhibition of oxygen-induced hypoxia-inducible factor-1alpha degradation unmasks estradiol induction of vascular endothelial growth factor expression in ECC-1 cancer cells in vitro. Endocrinology 150:5405-14
Pepe, Gerald J; Lynch, Terrie J; Davies, William A et al. (2009) Regulation of baboon fetal pituitary prolactin expression by estrogen. Biol Reprod 80:1189-95
Babischkin, Jeffery S; Bonagura, Thomas W; Udoff, Laurence C et al. (2009) Estrogen stimulates the human endometrium to express a factor(s) that promotes vascular smooth muscle cell migration as an early step in microvessel remodeling. Endocrine 35:81-8
Albrecht, Eugene D; Lane, Malcolm V; Marshall, Gary R et al. (2009) Estrogen promotes germ cell and seminiferous tubule development in the baboon fetal testis. Biol Reprod 81:406-14
Rockwell, L Christie; Koos, Robert D (2009) Dexamethasone enhances fertility and preovulatory serum prolactin levels in eCG/hCG primed immature rats. J Reprod Dev 55:247-51

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