? Virginia Commonwealth University (VCU) and the University of Chile will jointly offer translational research training in reproductive biology to junior scientists from throughout Latin America. Specific projects include: 1) Neutrophil induced epigenetic changes in vascular smooth muscle genes:
the aim i s to determine if neutrophils or neutrophil products (ROS, TNF??) can induce epigenetic changes in vascular smooth muscle genes related to inflammation and vascular dysfunction. The significance of these studies relates to the increased risk obese and preeclamptic women have of developing cardiovascular disease later in life. Studies will be conducted with human vascular smooth muscle cells co-cultured with activated neutrophils or neutrophils products (ROS, TNF??) to test the hypothesis that exposure of vascular smooth muscle cells to neutrophils, ROS or TNF-alpha will alter the DNA methylation pattern resulting in altered expression of genes and proteins relating to inflammation. 2) Transient expression of the progesterone receptor (PR) in follicular granulosa cells at the time of LH peak in normal ovulatory patients and after hCG administration of IVF patients:
the aim of this study is to determine if cytokines selectively down regulate PR of granulose cells, and are based on prior in vitro and in vivo studies regarding the role of PR expression at the time of ovulation. This includes a study in women confirming that the release of the LH surge from the pituitary induces a rapid cascade of signaling events resulting in the expression PR mRNA in granulosa cells of the follicle. New findings regarding genes regulating ovulation in humans may provide a key insight into anovulatory defects and to develop new strategies for emergency contraception. 3) Glucose transporters and matrix metalloproteinase 2 in the endometrium of women with PCOS: the hypothesis to be tested is that distortion of endometrial expression of glucose transporters and MMP2 in PCOS women alters endometrial metabolism and tissue remodeling, which are critical pathways for the establishment of a receptive endometrium and sustain an early pregnancy. Findings from this study have implications for improving implantation (and hence fertility) in PCOS and preventing early miscarriage Additional distance education offerings led by presenters from VCU and Chile will cover research areas covered by training mentors, including polycystic ovary syndrome and insulin resistance, preterm birth, pre-eclampsia, fetal membrane rupture, cell signaling, gonorrhea vaccine development, steroidogenesis, and promotion of healthy pregnancy. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Fogarty International Center (FIC)
Type
International Research Training Grants (D43)
Project #
5D43TW007692-02
Application #
7290359
Study Section
Special Emphasis Panel (ZRG1-BDA-A (90))
Program Officer
Mcdermott, Jeanne
Project Start
2006-09-22
Project End
2011-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
2
Fiscal Year
2007
Total Cost
$134,057
Indirect Cost
Name
Virginia Commonwealth University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Mousa, Ahmad A; Archer, Kellie J; Cappello, Renato et al. (2012) DNA methylation is altered in maternal blood vessels of women with preeclampsia. Reprod Sci 19:1332-42
Wang, Jiannan; Teves, Maria E; Shen, Xuening et al. (2012) Mouse RC/BTB2, a member of the RCC1 superfamily, localizes to spermatid acrosomal vesicles. PLoS One 7:e39846
Mousa, Ahmad A; Cappello, Renato E; Estrada-Gutierrez, Guadalupe et al. (2012) Preeclampsia is associated with alterations in DNA methylation of genes involved in collagen metabolism. Am J Pathol 181:1455-63
Nagarkatti-Gude, David R; Jaimez, Ruth; Henderson, Scott C et al. (2011) Spag16, an axonemal central apparatus gene, encodes a male germ cell nuclear speckle protein that regulates SPAG16 mRNA expression. PLoS One 6:e20625
Estrada-Gutierrez, Guadalupe; Cappello, Renato E; Mishra, Nikita et al. (2011) Increased expression of matrix metalloproteinase-1 in systemic vessels of preeclamptic women: a critical mediator of vascular dysfunction. Am J Pathol 178:451-60
Nestler, John E (2008) Metformin in the treatment of infertility in polycystic ovarian syndrome: an alternative perspective. Fertil Steril 90:14-6
Nestler, John E (2008) Metformin for the treatment of the polycystic ovary syndrome. N Engl J Med 358:47-54
Del Canto, Felipe; Sierralta, Walter; Kohen, Paulina et al. (2007) Features of natural and gonadotropin-releasing hormone antagonist-induced corpus luteum regression and effects of in vivo human chorionic gonadotropin. J Clin Endocrinol Metab 92:4436-43