Endometriosis is a common disorder that inflicts pain and suffering and is often the cause of infertility in women. There is a consensus that retrograde menstruation may account for the presence of endometrial cells in the peritoneal cavity. However, little is known regarding the etiology of the disease or why the disease occurs only in certain women despite the common occurrence of retrograde menstruation in most women. This program has five projects that propose novel hypotheses regarding the events that may lead to the establishment of endometriosis lesions. These ideas are extended as innovative specific aims that would be addressed using biochemical, immunological, and molecular biological techniques. Project 1 proposes that fundamental alterations in endometrial cell and macrophage scavenger functions to the peritoneal cavity of women with endometriosis are responsible for the survival and growth of the ectopic endometrium. Project 2 proposes an active mechanism by which intrinsic components of the peritoneal fluid may exacerbate an oxidative milieu that is conducive to the recruitment of mononuclear cells and the growth of the endometrial cells. This project suggests the presence of mildly oxidized lipoprotein components in the peritoneal fluid. Project 3 proposes that CSF-1 may play both autocrine and paracrine roles in promoting not only the growth of the endometrial cells but also in protecting macrophages from apoptotic death thereby increasing their survival in the peritoneal cavity. Project 4 will study the pharmacological regulation of macrophage scavenger function, production of cytokines, and endometrial cell growth. The effects of antioxidants, hormones, and retinoids on these functions will be determined. Project 5, the mini clinical project will establish the presence and differences in the markers of oxidative stress in the plasma of endometriosis subjects and controls. This project will also evaluate the efficacy of antioxidants to alter the levels of these markers. The program is supported by an administrative core and a tissue/cell culture core.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD035276-03
Application #
6329953
Study Section
Special Emphasis Panel (ZHD1-DRG-H (SP))
Program Officer
Parrott, Estella C
Project Start
1998-12-01
Project End
2003-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
3
Fiscal Year
2001
Total Cost
$783,721
Indirect Cost
Name
Emory University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Santanam, Nalini; Zoneraich, Nathaniel; Parthasarathy, Sampath (2017) Myeloperoxidase as a Potential Target in Women With Endometriosis Undergoing IVF. Reprod Sci 24:619-626
Santanam, Nalini; Kavtaradze, Nino; Murphy, Ana et al. (2012) Antioxidant supplementation reduces endometriosis-related pelvic pain in humans. Transl Res :
Budrys, Nicole M; Nair, Hareesh B; Liu, Ya-Guang et al. (2012) Increased expression of macrophage colony-stimulating factor and its receptor in patients with endometriosis. Fertil Steril 97:1129-35.e1
Griffith, Jason S; Binkley, Peter A; Kirma, Namir B et al. (2010) Imatinib decreases endometrial stromal cell transmesothial migration and proliferation in the extracellular matrix of modeled peritoneum. Fertil Steril 94:2531-5
Park, John K; Song, MingQing; Dominguez, Celia E et al. (2006) Glycodelin mediates the increase in vascular endothelial growth factor in response to oxidative stress in the endometrium. Am J Obstet Gynecol 195:1772-7
Cao, Xuan; Yang, Dongzi; Song, Mingqing et al. (2004) The presence of endometrial cells in the peritoneal cavity enhances monocyte recruitment and induces inflammatory cytokines in mice: implications for endometriosis. Fertil Steril 82 Suppl 3:999-1007
Wanichkul, Thitikorn; Han, Shouwei; Huang, Ruo-Pan et al. (2003) Cytokine regulation by peroxisome proliferator-activated receptor gamma in human endometrial cells. Fertil Steril 79 Suppl 1:763-9
Han, Shouwei; Inoue, Hiroyasu; Flowers, Lisa C et al. (2003) Control of COX-2 gene expression through peroxisome proliferator-activated receptor gamma in human cervical cancer cells. Clin Cancer Res 9:4627-35
Song, Mingqing; Karabina, Sonia A; Kavtaradze, Nino et al. (2003) Presence of endometrial epithelial cells in the peritoneal cavity and the mesothelial inflammatory response. Fertil Steril 79 Suppl 1:789-94
Han, Shouwei; Sidell, Neil (2003) RU486-induced growth inhibition of human endometrial cells involves the nuclear factor-kappa B signaling pathway. J Clin Endocrinol Metab 88:713-9

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