Abstract

This application is built on the hypothesis that coordinated changes in the expression of specific MMPs and their inhibitors produce alterations in the fetal membranes that lead to their rupture under normal and pathological conditions.
Aim 1 is to characterize amnion type I and type IV collagen fragmentation patterns.
Aim 2 is to determine if mutations in collagen chains affect the structural dissolution of the amnion at term.
Aim 3 is to define the temporal and spatial patterns of expression of MMPs capable of degrading interstitial and type IV collagens in the rat amnion.
Aim 4 is to determine if MMP inhibitors and antisense oligonucleotides directed against specific MMPs prevent structural changes in the amnion.
Aim 5 is to determine if the induction of MMPs and changes in the amnion are dependent on gestational age.
Aim 6 is to determine if withdrawal of progesterone induces MMP activities and the terminal changes in amnion structure.
Aim 7 is to identify amnion-specific genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD034612-02
Application #
2403626
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1996-09-30
Project End
2001-08-31
Budget Start
1997-09-01
Budget End
1998-08-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

York, Timothy P; Eaves, Lindon J; Neale, Michael C et al. (2014) The contribution of genetic and environmental factors to the duration of pregnancy. Am J Obstet Gynecol 210:398-405
Strauss 3rd, Jerome F (2013) Extracellular matrix dynamics and fetal membrane rupture. Reprod Sci 20:140-53
York, Timothy P; Eaves, Lindon J; Lichtenstein, Paul et al. (2013) Fetal and maternal genes' influence on gestational age in a quantitative genetic analysis of 244,000 Swedish births. Am J Epidemiol 178:543-50
Hill, Lori D; Hilliard, DaShaunda D; York, Timothy P et al. (2011) Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study. BMC Med Genet 12:64
Negorev, Dmitri G; Vladimirova, Olga V; Kossenkov, Andrew V et al. (2010) Sp100 as a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program. Cancer Res 70:9991-10001
Harwich Jr, Michael D; Alves, Joao M; Buck, Gregory A et al. (2010) Drawing the line between commensal and pathogenic Gardnerella vaginalis through genome analysis and virulence studies. BMC Genomics 11:375
York, Timothy P; Strauss 3rd, Jerome F; Neale, Michael C et al. (2010) Racial differences in genetic and environmental risk to preterm birth. PLoS One 5:e12391
Anum, Emmanuel A; Brown, Haywood L; Strauss 3rd, Jerome F (2010) Health disparities in risk for cervical insufficiency. Hum Reprod 25:2894-900
Ferrell, Georgia; Lu, Minyan; Stoddard, Paul et al. (2009) A single nucleotide polymorphism in the promoter of the LOXL1 gene and its relationship to pelvic organ prolapse and preterm premature rupture of membranes. Reprod Sci 16:438-46
Anum, E A; Hill, L D; Pandya, A et al. (2009) Connective tissue and related disorders and preterm birth: clues to genes contributing to prematurity. Placenta 30:207-15

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