Research Topics
Genomes and GenesSpecies | Graciela KrikunSummaryAffiliation: Yale University Country: USA Publications
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Publications
Endometrial angiogenesis: from physiology to pathologyG Krikun
Yale University School of Medicine, Department of Ob Gyn, 333 Cedars Street, P O Box 208063, New Haven, CT 06520 8063, USA
Ann N Y Acad Sci 1034:27-35. 2004..Particular emphasis is placed on the expression of the angiopoietins and their physiological and pathological expression...- Endometrial angiopoietin expression and modulation by thrombin and steroid hormones: a mechanism for abnormal angiogenesis following long-term progestin-only contraceptionGraciela Krikun
Department of Obstetrics, Yale University, School of Medicine, New Haven, Connecticut 06520 8063, USA
Am J Pathol 164:2101-7. 2004.... - Endometriosis and tissue factorGraciela Krikun
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine 333 Cedar St, P O Box 208063, New Haven, CT, 06520 8063, USA
Ann N Y Acad Sci 1127:101-5. 2008..Thus, our studies suggest that TF might be an ideal target for therapeutic intervention in endometriosis... - Thrombin activation of endometrial endothelial cells: a possible role in intrauterine growth restrictionGraciela Krikun
Department of Obstetrics, Gynecology and Reproductive Science, Yale University, School of Medicine, New Haven, CT 06520 8063, USA
Thromb Haemost 97:245-53. 2007..Thus, we postulate that reductions in uteroplacental flow initiate a cascade of molecular effects leading to hypoxia, thrombosis, inflammation, and endothelial cell dysfunction resulting in untoward pregnancy outcomes... - Expression of Toll-like receptors in the human deciduaG Krikun
The Department of Obstetrics, Gynecology and Reproductive Science, School of Medicine, New Haven, CT 06520 8063, USA
Histol Histopathol 22:847-54. 2007..In contrast to the growing evidence that the immune surveillance molecules known as Toll-like receptors (TLRs) are expressed by trophoblasts and fetal membranes, to date, no studies have been conducted on the decidua... - Metalloproteinase expression by control and telomerase immortalized human endometrial endothelial cellsG Krikun
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 8063, USA
Histol Histopathol 20:719-24. 2005..The levels of MMP expression as well as that of the metalloprotease inhibitors TIMP-1 and TIMP-2 were similar in parent and immortalized endothelial cells... - Endometrial endothelial cell steroid receptor expression and steroid effects on gene expressionGraciela Krikun
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, P O Box 208063, New Haven, Connecticut 06520 8063, USA
J Clin Endocrinol Metab 90:1812-8. 2005..Thus, quantitative RT-PCR and microarray analyses demonstrate that HEECs express ER-beta and PR mRNA and that gene expression by HEECs is differentially regulated by treatment with estrogen or progestin... - Tissue factor and the endometrium: from physiology to pathologyGraciela Krikun
Department of Ob Gyn, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
Thromb Res 124:393-6. 2009..Below we describe the latest findings of the expression and function of TF as well as its specific role in physiologic or pathologic conditions of the human endometrium... - A novel immortalized human endometrial stromal cell line with normal progestational responseGraciela Krikun
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, P O Box 208063, New Haven, Connecticut 06520 8063, USA
Endocrinology 145:2291-6. 2004..In summary, an immortalized HESC line has been developed that is karyotypically, morphologically, and phenotypically similar to the primary parent cells, and it is a powerful and consistent resource for in vitro work... - The immunoconjugate "icon" targets aberrantly expressed endothelial tissue factor causing regression of endometriosisGraciela Krikun
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT 06520 8063, USA
Am J Pathol 176:1050-6. 2010..Thus, Icon could serve as a novel, nontoxic, fertility-preserving, and effective treatment for endometriosis... - Abnormal uterine bleeding during progestin-only contraception may result from free radical-induced alterations in angiopoietin expressionGraciela Krikun
Department of Obstetrics and Gynecology, New York University Medical Center, New York, USA
Am J Pathol 161:979-86. 2002.... - Long-term progestin-only contraception in humans versus animal modelsGraciela Krikun
Department of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut, USA
Ann N Y Acad Sci 1221:119-23. 2011..In this review, we describe these models including the guinea pig, an animal model we have previously investigated, to assess the mechanisms involved in abnormal uterine bleeding following long-term progestin-only contraception... - Steroid hormones, endometrial gene regulation and the Sp1 family of proteinsGraciela Krikun
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA
J Soc Gynecol Investig 9:329-34. 2002.... - Long-term progestin contraceptives (LTPOC) induce aberrant angiogenesis, oxidative stress and apoptosis in the guinea pig uterus: A model for abnormal uterine bleeding in humansGraciela Krikun
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06510, USA
J Angiogenes Res 2:8. 2010..However, obtaining sufficient, good quality tissues have precluded elucidation of the mechanisms underlying these morphological and functional vascular changes... - Decidualized human endometrial stromal cells mediate hemostasis, angiogenesis, and abnormal uterine bleedingCharles J Lockwood
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
Reprod Sci 16:162-70. 2009..The resulting enhanced vessel fragility promotes abnormal uterine bleeding... - Thrombin regulates soluble fms-like tyrosine kinase-1 (sFlt-1) expression in first trimester decidua: implications for preeclampsiaCharles J Lockwood
The Anita O Keefe Young Professor and Chair, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, Room 335 FMB, P O Box 208063, New Haven, CT, USA
Am J Pathol 170:1398-405. 2007..In early pregnancy, thrombin may act as an autocrine/paracrine enhancer of sFlt-1 expression by decidual cells to promote pre-eclampsia by interfering with local vascular transformation... - Regulation of monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha and interleukin-1beta in first trimester human decidual cells: implications for preeclampsiaCharles J Lockwood
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA
Am J Pathol 168:445-52. 2006..This finding suggests a mechanism by which recruitment of excess macrophages to the decidua impairs endovascular trophoblast invasion, the primary placental defect of preeclampsia... - Progestin-regulated expression of tissue factor in decidual cells: implications in endometrial hemostasis, menstruation and angiogenesisFrederick Schatz
Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, Room 335 FMB, P O Box 208063, New Haven, CT 06520 8063, USA
Steroids 68:849-60. 2003..Since thrombin and VEGF induce angiogenesis via separate endothelial cell receptors, they may synergize to elicit aberrant angiogenesis, and ultimately lead to focal bleeding... - Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term deciduaCharles J Lockwood
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar St, PO Box 208063, Room 334FMB, New Haven, CT 06520 8063, USA
Am J Pathol 167:1443-9. 2005..In summary, thrombin-enhanced IL-8 expression in term decidual cells may explain how abruption-associated PPROM promotes decidual neutrophil infiltration... - Decidual cell-expressed tissue factor in human pregnancy and its involvement in hemostasis and preeclampsia-related angiogenesisCharles J Lockwood
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, Room 335 FMB, P O Box 208063, New Haven, CT, 06510, USA
Ann N Y Acad Sci 1127:67-72. 2008.... - Tibolone and its metabolites enhance tissue factor and PAI-1 expression in human endometrial stromal cells: Evidence of progestogenic effectsFrederick Schatz
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 8063, USA
Steroids 70:840-5. 2005..Since TF and PAI-1 promote hemostasis by complementary mechanisms, our findings account for the reduced occurrence of abnormal uterine bleeding associated with tibolone therapy... - Tumor necrosis factor-alpha and interleukin-1beta regulate interleukin-8 expression in third trimester decidual cells: implications for the genesis of chorioamnionitisCharles J Lockwood
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, Room 335 FMB P O Box 208063 New Haven, CT
Am J Pathol 169:1294-302. 2006.... - Intercellular adhesion molecule-1 expression in human endometrium: implications for long term progestin only contraceptionFrederick Schatz
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
Reprod Biol Endocrinol 4:2. 2006.... - Effects of thrombin, hypoxia, and steroids on interleukin-8 expression in decidualized human endometrial stromal cells: implications for long-term progestin-only contraceptive-induced bleedingCharles J Lockwood
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
J Clin Endocrinol Metab 89:1467-75. 2004..However, LTPOC-induced hypoxia and excess thrombin generation enhance IL-8 expression in decidualized HESCs, thereby eliciting aberrant angiogenesis and inflammation that promote the onset of abnormal uterine bleeding... - The role of decidualization in regulating endometrial hemostasis during the menstrual cycle, gestation, and in pathological statesCharles J Lockwood
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06511, USA
Semin Thromb Hemost 33:111-7. 2007..In association with long-term progestin-only contraception, overexpression of decidual cell-derived thrombin promotes aberrant angiogenesis and vessel maintenance to contribute to abnormal uterine bleeding... - Decidual hemostasis, inflammation, and angiogenesis in pre-eclampsiaCharles J Lockwood
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06510, USA
Semin Thromb Hemost 37:158-64. 2011.... - Tibolone exerts progestational inhibition of matrix metalloproteinase expression in human endometrial stromal cellsFrederick Schatz
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street Room 334 FMB, PO Box 208063, New Haven, CT 06520 8063, USA
Steroids 71:768-75. 2006..These observations help to explain the paradox that the endometrium becomes atrophic after tibolone administration despite the persistence in the circulation of 3alpha-OH and 3beta-OH tibolone, but not tibolone or Delta-4 tibolone... - Inflammatory cytokine and thrombin regulation of interleukin-8 and intercellular adhesion molecule-1 expression in first trimester human deciduaCharles J Lockwood
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, Room 335 FMB P O Box 208063, New Haven, Connecticut 06510, USA
J Clin Endocrinol Metab 90:4710-5. 2005..Transendothelial neutrophil migration into inflamed tissues involves IL-8-mediated chemoattraction, then neutrophil attachment to endothelial cell-expressed intercellular adhesion molecule-1 (ICAM-1)... - Thrombin regulates monocyte chemoattractant protein-1 expression in human first trimester and term decidual cellsPaul Matta
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
Am J Obstet Gynecol 196:268.e1-8. 2007..Therefore, the current study evaluated whether thrombin affects monocyte chemoattractant protein-1 (MCP-1) expression in stromal cells that are derived from cycling and gestational endometrium... - Differential cell-specific modulation of HOXA10 by estrogen and specificity protein 1 response elementsRyan Martin
Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520 8063, USA
J Clin Endocrinol Metab 92:1920-6. 2007..HOX genes are highly evolutionarily conserved regulators of embryonic development. HOXA10 also regulates differentiation of the adult reproductive tract and mammary gland in response to sex steroids... - Mechanisms of abruption-induced premature rupture of the fetal membranes: Thrombin enhanced decidual matrix metalloproteinase-3 (stromelysin-1) expressionAndrew P Mackenzie
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA
Am J Obstet Gynecol 191:1996-2001. 2004.... - The immortalization of human endometrial cellsGraciela Krikun
Department of Obstetrics and Gynecology, Yale University, New Haven, CT, USA
Methods Mol Med 121:79-83. 2006..In this article, we will address this approach in the establishment of immortalized endometrial cells and its value in facilitating in vitro studies... - The placental syncytium and the pathophysiology of preeclampsia and intrauterine growth restriction: a novel assay to assess syncytial protein expressionSeth Guller
Department of Obstetrics Gynecology, Yale University School of Medicine, 333 Cedar Street, 339 FMB, P O Box 208063, New Haven, CT 06520 8063, USA
Ann N Y Acad Sci 1127:129-33. 2008.... - Preimplantation factor promotes first trimester trophoblast invasionChristina M Duzyj
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale Women and Children s Center for Blood Disorders, New Haven, CT 06520 8063, USA
Am J Obstet Gynecol 203:402.e1-4. 2010..Herein, we explore the effects of synthetic preimplantation factor on trophoblast invasion... - A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cellsMichael J Paidas
Yale Women and Children s Center for Blood Disorders, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520 8063, USA
Am J Obstet Gynecol 202:459.e1-8. 2010..This study aims to elucidate PIF's effects in human endometrial stromal cells (HESC) decidualized by estrogen and progestin, which mimics the preimplantation milieu, and in first-trimester decidua cultures (FTDC)... - Differential effects of thrombin and hypoxia on endometrial stromal and glandular epithelial cell vascular endothelial growth factor expressionCharles J Lockwood
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York 10016, USA
J Clin Endocrinol Metab 87:4280-6. 2002..Because angiogenesis occurs in a matrix of decidualized HESCs, these in vitro results provide a novel mechanism to account for both the peak in VEGF and angiogenesis in luteal phase human endometrium... - A novel three-dimensional in vitro system to study trophoblast-endothelium cell interactionsPaulomi B Aldo
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Yale University, New Haven, CT 06520, USA
Am J Reprod Immunol 58:98-110. 2007..We describe a novel in vitro model to evaluate endothelial-trophoblast interaction and signaling in a three-dimensional system... - Novel insights into molecular mechanisms of abruption-induced preterm birthCatalin S Buhimschi
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
Expert Rev Mol Med 12:e35. 2010..Here, we provide novel insights into the molecular mechanisms and pathways leading to PTB in the setting of placental abruption... - Novel therapies targeting endometriosisHugh S Taylor
Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University, 333 Cedar Street, New Haven, CT 06520, USA
Reprod Sci 18:814-23. 2011..The most promising of these potential therapies are currently slated for further testing in both rodent and nonhuman primate trials... - Preeclampsia-related inflammatory cytokines regulate interleukin-6 expression in human decidual cellsCharles J Lockwood
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520 8063, USA
Am J Pathol 172:1571-9. 2008.... - Regulation of chemokine production in response to pro-inflammatory cytokines in first trimester decidual cellsS J Huang
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT 06510, USA
J Reprod Immunol 72:60-73. 2006.... - Effects of etonogestrel treatment in the reproductive organs and uterine arteries of nonoophorectomized Guinea pigsGraciela Krikun
1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT, USA
Reprod Sci 19:400-6. 2012..Lastly, effects on vasomotor features of uterine arteries suggest changes that favor increased resistance and reduced blood flow promoting decreased ability to withstand elevations in transmural pressure... - Preeclampsia, hypoxia, thrombosis, and inflammationAmir A Shamshirsaz
Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, CT 06520, USA
J Pregnancy 2012:374047. 2012..In this review, we detail these effects and their relationship to preeclampsia (PE) and intrauterine growth restriction (IUGR)... - Cell type-specific expression and function of toll-like receptors 2 and 4 in human placenta: implications in fetal infectionY Ma
Department of Obstetrics Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street 339 FMB, PO Box 208063, New Haven, CT 06520 8063, USA
Placenta 28:1024-31. 2007..Our results indicate that there exist cell type-specific patterns of TLR function in placenta which likely regulate innate immune response at the maternal-fetal interface... - Decidual cell-expressed tissue factor maintains hemostasis in human endometriumC J Lockwood
Department of Obstetrics and Gynecology, New York University School of Medicine, New York 10016, USA
Ann N Y Acad Sci 943:77-88. 2001..The absence of canonical estrogen and progesterone response elements from either the TF or Sp1 gene promoters suggests that the EGFR may help to mediate progestin-enhanced TF expression during decidualization of HESCs... - Expression of angiopoietin-2 by human endometrial endothelial cells: regulation by hypoxia and inflammationG Krikun
Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, 10016, USA
Biochem Biophys Res Commun 275:159-63. 2000..Both hypoxia and phorbol-myristate-acetate enhanced Ang-2 mRNA levels in HEECs. These results suggest that Ang-2 plays a role in endometrial pathologies complicated by impaired blood flow and inflammation... - Angiogenic factors and the endometrium following long term progestin only contraceptionC J Lockwood
Department of OB/GYN, Yale University School of Medicine, New Haven, CT 06520-8063, USA
Histol Histopathol 19:167-72. 2004..Studies in this area offer a promising avenue to alleviate abnormal uterine bleeding associated with this otherwise highly effective form of contraception.. - Long-term progestin-only contraceptives result in reduced endometrial blood flow and oxidative stressM Hickey
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, 333 Cedar Street, New Haven, Connecticut, 06520-8063, USA
J Clin Endocrinol Metab 91:3633-8. 2006..MAIN OUTCOME: LTPOC treatment resulted in reduced endometrial perfusion and increased endometrial oxidative damage. CONCLUSIONS: We propose that LTPOCs result in hypoxia reperfusion, which leads to aberrant angiogenesis resulting in AUB... - The role of tissue factor in regulating endometrial haemostasis: implications for progestin-only contraceptionC J Lockwood
Department of Obstetrics and Gynecology, New York University School of Medicine, NY 10016, USA
Hum Reprod 15:144-51. 2000.... - Biological mechanisms underlying the clinical effects of mifepristone (RU 486) on the endometriumC Papp
1st Department of Obstetrics and Gynecology Semmelweis University, Budapest and Department of Obstetrics and Gynecology, New York University Medical Center, New York, USA
Early Pregnancy 4:230-9. 2000..In this review we sought to summarize the biological mechanisms underlying the clinical effects of RU 486 on endometrial haemorrhage/haemostasis and on ECM degradation... - Involvement of human decidual cell-expressed tissue factor in uterine hemostasis and abruptionC J Lockwood
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520, USA
Thromb Res 124:516-20. 2009.... - Regulation of tissue factor gene expression in human endometrium by transcription factors Sp1 and Sp3G Krikun
The Department of Obstetrics and Gynecology, New York University School of Medicine, Tisch Hospital, New York 10016, USA
Mol Endocrinol 14:393-400. 2000..We propose that progestins regulate HESC TF gene expression in vivo by altering the ratio of Sp1 to Sp3 nuclear factors... - Progestin and thrombin regulate tissue factor expression in human term decidual cellsC J Lockwood
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520, USA
J Clin Endocrinol Metab 94:2164-70. 2009..The identity and potential regulation of TF-expressing cells at the human maternal-fetal interface that confers hemostatic protection during normal and preterm delivery is unclear...