.

Department of Pathology, Microbiology, and Immunology

 

 

   Kevin G. Osteen, Ph.D.

 

  

Professor,

Dept of Obstetrics and Gynecology

Dept of Pathology, Microbiology and Immunology

 Director, Women’s Reproductive Health Research Center

 

  Contact Information

 

 

Office Location:

S-121 MCN

Phone: 615-322-4196

E-mail: kevin.osteen@vanderbilt.edu

Campus Mail address:

Department  of Obstetrics and Gynecology

B-1100 MCN (2519)

 

US Mailing address:

Vanderbilt University School of Medicine

Dept Obstetrics and Gynecology

B-1100 MCN

Nashville, TN 37232-2519

 

 

 

Education

 

 

Fellowship, Univ. of MD, Baltimore MD
Ph.D., Medical College of GA, Augusta GA
B.S., Univ. of SC, Columbia SC

 

 

Research Keywords

 

 

reproductive medicine, human endometium, endometrial dysfunction, endometriosis, progesterone action, environmental endocrine disruptors, developmental exposure

 

 

Research Description

 

 

Among normal adult tissues, the endometrial lining of the human uterus undergoes perhaps the most dynamic cycle of steroid controlled growth, differentiation and tissue breakdown. The rate of estrogen-driven cell growth during the proliferative phase of the menstrual cycle rivals that of many tumors while progesterone inhibits endometrial growth and appears to provide protection from the development of both benign diseases and certain neoplasms. Ovarian steroids clearly control the endometrium and endometrial activity; however, steroids alone cannot account for the entire orchestration of such well-controlled and often focal patterns of cellular proliferation and differentiation which are observed. To better understand steroid sensitive tissue behavior, my research laboratory has focused on the endometrium as a model to identify interrelationships between steroid action and stromal-epithelial cell communication via specific paracrine factors. Of special interest to us are the cellular and molecular mechanisms which control steroid-dependent versus steroid-independent expressions of metalloproteinases. These enzymes are necessary for degradation of extracellular matrix proteins and play important roles in the extensive tissue remodeling which normally occurs during the menstrual cycle as well as during establishment of the hemochorial placenta. Metalloproteinases may also contribute to the pathophysiology of endometrial dysfunction including abnormal bleeding, defects of placentation and the extrauterine disease endometriosis. Recently, we have extended our studies to investigate altered metalloproteinase gene and protein expression relative to the reproductive toxicology of dioxin.

 

 

Publications

 

 

Halder, SK, Osteen, KG, Al-Hendy, A. Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells. Hum Reprod, 28(9), 2407-16, 2013

Herington, JL, Glore, DR, Lucas, JA, Osteen, KG, Bruner-Tran, KL. Dietary fish oil supplementation inhibits formation of endometriosis-associated adhesions in a chimeric mouse model. Fertil Steril, 99(2), 543-50, 2013

Sokalska, A, Anderson, M, Villanueva, J, Ortega, I, Bruner-Tran, KL, Osteen, KG, Duleba, AJ. Effects of simvastatin on retinoic acid system in primary human endometrial stromal cells and in a chimeric model of human endometriosis. J Clin Endocrinol Metab, 98(3), E463-71, 2013

Villanueva, JA, Sokalska, A, Cress, AB, Ortega, I, Bruner-Tran, KL, Osteen, KG, Duleba, AJ. Resveratrol potentiates effect of simvastatin on inhibition of mevalonate pathway in human endometrial stromal cells. J Clin Endocrinol Metab, 98(3), E455-62, 2013

Halder, SK, Osteen, KG, Al-Hendy, A. 1,25-dihydroxyvitamin d3 reduces extracellular matrix-associated protein expression in human uterine fibroid cells. Biol Reprod, 89(6), 150, 2013

Bruner-Tran, KL, Herington, JL, Duleba, AJ, Taylor, HS, Osteen, KG. Medical management of endometriosis: emerging evidence linking inflammation to disease pathophysiology. Minerva Ginecol, 65(2), 199-213, 2013

Bruner-Tran, KL, Resuehr, D, Ding, T, Lucas, JA, Osteen, KG. The Role of Endocrine Disruptors in the Epigenetics of Reproductive Disease and Dysfunction: Potential Relevance to Humans. Curr Obstet Gynecol Rep, 1(3), 116-123, 2012

Cakmak, H, Basar, M, Seval-Celik, Y, Osteen, KG, Duleba, AJ, Taylor, HS, Lockwood, CJ, Arici, A. Statins inhibit monocyte chemotactic protein 1 expression in endometriosis. Reprod Sci, 19(6), 572-9, 2012

Resuehr, D, Glore, DR, Taylor, HS, Bruner-Tran, KL, Osteen, KG. Progesterone-dependent regulation of endometrial cannabinoid receptor type 1 (CB1-R) expression is disrupted in women with endometriosis and in isolated stromal cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Fertil Steril, 98(4), 948-56.e1, 2012

Sokalska, A, Cress, A, Bruner-Tran, KL, Osteen, KG, Taylor, HS, Ortega, I, Duleba, AJ. Simvastatin decreases invasiveness of human endometrial stromal cells. Biol Reprod, 87(1), 2, 1-6, 2012

McConaha, ME, Ding, T, Lucas, JA, Arosh, JA, Osteen, KG, Bruner-Tran, KL. Preconception omega-3 fatty acid supplementation of adult male mice with a history of developmental TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) exposure prevents preterm birth in unexposed female partners. Reproduction, 2011

Herington, JL, Bruner-Tran, KL, Lucas, JA, Osteen, KG. Immune interactions in endometriosis. Expert Rev Clin Immunol, 7(5), 611-26, 2011

Taylor, HS, Osteen, KG, Bruner-Tran, KL, Krikun, G, Sokalska, A, Duleba, AJ. Novel Therapies Targeting Endometriosis. Reprod Sci, 2011

Bruner-Tran, KL, Osteen, KG. Dioxin-like PCBs and endometriosis. Syst Biol Reprod Med, 56(2), 132-46, 2010

Bruner-Tran, KL, Carvalho-Macedo, AC, Duleba, AJ, Crispens, MA, Osteen, KG. Experimental endometriosis in immunocompromised mice after adoptive transfer of human leukocytes. Fertil Steril, 93(8), 2519-24, 2010

Bruner-Tran, K, Osteen, KG, Taylor, HS, Sokalska, A, Haines, K, Duleba, AJ. Resveratrol Inhibits Development of Experimental Endometriosis In Vivo and Reduces Endometrial Stromal Cell Invasiveness In Vitro. Biol Reprod, 2010

Krikun, G, Hu, Z, Osteen, K, Bruner-Tran, KL, Schatz, F, Taylor, HS, Toti, P, Arcuri, F, Konigsberg, W, Garen, A, Booth, CJ, Lockwood, CJ. The immunoconjugate "icon" targets aberrantly expressed endothelial tissue factor causing regression of endometriosis. Am J Pathol, 176(2), 1050-6, 2010

Bruner-Tran, KL, Ding, T, Osteen, KG. Dioxin and endometrial progesterone resistance. Semin Reprod Med, 28(1), 59-68, 2010

Ding, T, McConaha, M, Boyd, KL, Osteen, KG, Bruner-Tran, KL. Developmental dioxin exposure of either parent is associated with an increased risk of preterm birth in adult mice. Reprod Toxicol, 2010

Bruner-Tran, KL, Osteen, KG. Developmental exposure to TCDD reduces fertility and negatively affects pregnancy outcomes across multiple generations. Reprod Toxicol, 2010

Herington, JL, Crispens, MA, Carvalho-Macedo, AC, Camargos, AF, Lebovic, DI, Bruner-Tran, KL, Osteen, KG. Development and prevention of postsurgical adhesions in a chimeric mouse model of experimental endometriosis. Fertil Steril, 2010

Bruner-Tran, KL, Osteen, KG, Duleba, AJ. Simvastatin protects against the development of endometriosis in a nude mouse model. J Clin Endocrinol Metab, 94(7), 2489-94, 2009

Bruner-Tran, KL, Yeaman, GR, Crispens, MA, Igarashi, TM, Osteen, KG. Dioxin may promote inflammation-related development of endometriosis. Fertil Steril, 89(5 Suppl), 1287-98, 2008

Nayyar, T, Bruner-Tran, KL, Piestrzeniewicz-Ulanska, D, Osteen, KG. Developmental exposure of mice to TCDD elicits a similar uterine phenotype in adult animals as observed in women with endometriosis. Reprod Toxicol, 23(3), 326-36, 2006

Bruner-Tran, KL, Zhang, Z, Eisenberg, E, Winneker, RC, Osteen, KG. Down-regulation of Endometrial MMP-3 and MMP-7 Expression in vitro and Therapeutic Regression of Experimental Endometriosis in vivo by a Novel Nonsteroidal Progesterone Receptor Agonist, Tanaproget. J Clin Endocrinol Metab, 91(4), 1554-60, 2006

Kurita, T, Medina, R, Schabel, AB, Young, P, Gama, P, Parekh, TV, Brody, J, Cunha, GR, Osteen, KG, Bruner-Tran, KL, Gold, LI. The activation function-1 domain of estrogen receptor alpha in uterine stromal cells is required for mouse but not human uterine epithelial response to estrogen. Differentiation, 73(6), 313-22, 2005

Osteen, KG, Bruner-Tran, KL, Eisenberg, E. Reduced progesterone action during endometrial maturation: a potential risk factor for the development of endometriosis. Fertil Steril, 83(3), 529-37, 2005

Osteen, KG, Bruner-Tran, KL, Eisenberg, E. Endometrial biology and the etiology of endometriosis. Fertil Steril, 84(1), 33-4; discussion 38-9, 2005

Igarashi, TM, Bruner-Tran, KL, Yeaman, GR, Lessey, BA, Edwards, DP, Eisenberg, E, Osteen, KG. Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fertil Steril, 84(1), 67-74, 2005

Harris, HA, Bruner-Tran, KL, Zhang, X, Osteen, KG, Lyttle, CR. A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosis. Hum Reprod, 20(4), 936-41, 2005

Osteen, KG, Igarashi, TM, Yeaman, GR, Bruner-Tran, KL. Steroid and cytokine regulation of matrix metalloproteinases and the pathophysiology of endometriosis. Gynecol Obstet Invest, 57(1), 53-4, 2004

Fortin M, Lepine M, Page M, Osteen K, Massie B, Hugo P, Steff A-M. An improved mouse model for endometriosis allows noninvasive assessment of lesion implantation and development. Fertil and Steril, 80,Suppl 2, 832-838, 2003

Hull, ML, Charnock-Jones, DS, Chan, CL, Bruner-Tran, KL, Osteen, KG, Tom, BD, Fan, TP, Smith, SK. Antiangiogenic agents are effective inhibitors of endometriosis. J Clin Endocrinol Metab, 88(6), 2889-99, 2003

Curry, TE, Osteen, KG. The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev, 24(4), 428-65, 2003

Fortin, M, L??pine, M, Pag??, M, Osteen, K, Massie, B, Hugo, P, Steff, AM. An improved mouse model for endometriosis allows noninvasive assessment of lesion implantation and development. Fertil Steril, 80 Suppl 2, 832-8, 2003

Osteen, Kevin G, Igarashi, Toshio M, Bruner-Tran, Kaylon L. Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression. Front Biosci, 8, d78-86, 2003

Apparao, KB, Illera MJ, Beyler SA, Olson GE, Osteen KG, Corjay MH, Boggess K, Lessey, BA. Regulated expression of osteopontin in the peri-implantation rabbit uterus. Biol Reprod, 68, 1484-1490, 2003

Hull ML, Charnock-Jones DS, Chan CL, Bruner-Tran KL, Osteen KG, Tom BD, Fan TP, Smith SK. Antiangiogenic agents are effective inhibitors of endometriosis. J Clin Endocrinol Metab, 88, 2889-2899, 2003

Osteen, Kevin G, Yeaman, Grant R, Bruner-Tran, Kaylon L. Matrix metalloproteinases and endometriosis. Semin Reprod Med, 21(2), 155-64, 2003

Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA, Giudice, LC. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology, 144, 2870-2881, 2003

Osteen, KG, Bruner-Tran, KL, Keller, NR, Eisenberg, E. Progesterone-mediated endometrial maturation limits matrix metalloproteinase (MMP) expression in an inflammatory-like environment: a regulatory system altered in endometriosis. Ann N Y Acad Sci, 955, 37-47; discussion 86-8, 396-406, 2002

Cornet PB, Picquet C, Lemoine P, Osteen KG, Bruner-Tran KL, Tabibzadeh S, Courtoy PJ, Eeckhout Y, Marbaix E, Henriet P. Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression during the menstrual cycle, control by progesterone, and effect on matrix metalloprotineases. Biol Chem , 277, 42496-42504, 2002

Bruner-Tran, KL, Webster-Clair, D, Osteen, KG. Experimental endometriosis: the nude mouse as a xenographic host. Ann N Y Acad Sci, 955, 328-39; discussion 340-2, 396-406, 2002

Osteen, KG, Bruner-Tran, KL, Ong, D, Eisenberg, E. Paracrine mediators of endometrial matrix metalloproteinase expression: potential targets for progestin-based treatment of endometriosis. Ann N Y Acad Sci, 955, 139-46; discussion 157-8, 396-406, 2002

Bruner-Tran, Kaylon L, Eisenberg, Esther, Yeaman, Grant R, Anderson, Ted A, McBean, Judith, Osteen, Kevin G. Steroid and cytokine regulation of matrix metalloproteinase expression in endometriosis and the establishment of experimental endometriosis in nude mice. J Clin Endocrinol Metab, 87(10), 4782-91, 2002

Bofinger DP, Feng L, Chi LH, Love J, Stephen FD, Sutter TR, Osteen KG, Costich TG, Batt RE, Koury ST, Olson JR. Effect of TCDD exposure on CYP1A1 and CYP1B1 expression in explant cultures of human endometrium. Toxicol Sci, 62, 299-314, 2001

Curry TE Jr, Osteen KG. Cyclic changes in the matrix metalloproteinase system in the ovary and uterus. Biol Reprod, 64, 1285-1296, 2001

Zheng, W L, Sierra-Rivera, E, Luan, J, Osteen, K G, Ong, D E. Retinoic acid synthesis and expression of cellular retinol-binding protein and cellular retinoic acid-binding protein type II are concurrent with decidualization of rat uterine stromal cells. Endocrinology, 141(2), 802-8, 2000

Keller, N R, Sierra-Rivera, E, Eisenberg, E, Osteen, K G. Progesterone exposure prevents matrix metalloproteinase-3 (MMP-3) stimulation by interleukin-1alpha in human endometrial stromal cells. J Clin Endocrinol Metab, 85(4), 1611-9, 2000

Bruner, K L, Eisenberg, E, Gorstein, F, Osteen, K G. Progesterone and transforming growth factor-beta coordinately regulate suppression of endometrial matrix metalloproteinases in a model of experimental endometriosis. Steroids, 64(9), 648-53, 1999

Osteen, K G, Keller, N R, Feltus, F A, Melner, M H. Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium. Gynecol Obstet Invest, 48 Suppl 1, 2-13, 1999

Bruner-Tran, K L, Rier, S E, Eisenberg, E, Osteen, K G. The potential role of environmental toxins in the pathophysiology of endometriosis. Gynecol Obstet Invest, 48 Suppl 1, 45-56, 1999

Zheng, W L, Bucco, R A, Sierra-Rievera, E, Osteen, K G, Melner, M H, Ong, D E. Synthesis of retinoic acid by rat ovarian cells that express cellular retinoic acid-binding protein-II. Biol Reprod, 60(1), 110-4, 1999

Bucco, R A, Zheng, W L, Davis, J T, Sierra-Rivera, E, Osteen, K G, Chaudhary, A K, Ong, D E. Cellular retinoic acid-binding protein(II) presence in rat uterine epithelial cells correlates with their synthesis of retinoic acid. Biochemistry, 36(13), 4009-14, 1997

Osteen, K G, Sierra-Rivera, E, Keller, N R, Fox, D B. Interleukin-1 alpha opposes progesterone-mediated suppression of MMP-7. A possible role of this cytokine during human implantation. Ann N Y Acad Sci, 828, 137-45, 1997

Osteen, K G, Sierra-Rivera, E. Does disruption of immune and endocrine systems by environmental toxins contribute to development of endometriosis. Semin Reprod Endocrinol, 15(3), 301-8, 1997

Bruner, K L, Matrisian, L M, Rodgers, W H, Gorstein, F, Osteen, K G. Suppression of matrix metalloproteinases inhibits establishment of ectopic lesions by human endometrium in nude mice. J Clin Invest, 99(12), 2851-7, 1997

Bucco, R A, Zheng, W L, Wardlaw, S A, Davis, J T, Sierra-Rivera, E, Osteen, K G, Melner, M H, Kakkad, B P, Ong, D E. Regulation and localization of cellular retinol-binding protein, retinol-binding protein, cellular retinoic acid-binding protein (CRABP), and CRABP II in the uterus of the pseudopregnant rat. Endocrinology, 137(7), 3111-22, 1996

Osteen, K G, Bruner, K L, Sharpe-Timms, K L. Steroid and growth factor regulation of matrix metalloproteinase expression and endometriosis. Semin Reprod Endocrinol, 14(3), 247-55, 1996

Bruner, K L, Rodgers, W H, Gold, L I, Korc, M, Hargrove, J T, Matrisian, L M, Osteen, K G. Transforming growth factor beta mediates the progesterone suppression of an epithelial metalloproteinase by adjacent stroma in the human endometrium. Proc Natl Acad Sci U S A, 92(16), 7362-6, 1995

Rodgers, WH, Matrisian, LM, Giudice, LC, Dsupin, B, Cannon, P, Svitek, C, Gorstein, F, and KG Osteen. Patterns of matrix metalloproteinase expression in cycling endometrium imply differential functions and regulation by steroids. J. Clin. Invest., 94, 946-953, 1994

Osteen, K G, Rodgers, W H, Gaire, M, Hargrove, J T, Gorstein, F, Matrisian, L M. Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium. Proc Natl Acad Sci U S A, 91(21), 10129-33, 1994

Matrisian, L M, Gaire, M, Rodgers, W H, Osteen, K G. Metalloproteinase expression and hormonal regulation during tissue remodeling in the cycling human endometrium. Contrib Nephrol, 107, 94-100, 1994

Rodgers, W H, Osteen, K G, Matrisian, L M, Navre, M, Giudice, L C, Gorstein, F. Expression and localization of matrilysin, a matrix metalloproteinase, in human endometrium during the reproductive cycle. Am J Obstet Gynecol, 168(1 Pt 1), 253-60, 1993

Vasquez, JM, Eisenberg, E, Osteen, KG, Hickerson, D, Diamond, MP. Laparoscopic ablation of endometriosis using the cavitational ultrasonic surgical aspirator. J Am Assoc Gynecol Laparosc, 1(1), 36-42, 1993

Bastias, MC, Kamijo, H, Osteen, KG. Assessment of human sperm functional changes after in-vitro coincubation with cells retrieved from the human female reproductive tract. Hum Reprod, 8(10), 1670-7, 1993

Freeman, MR, Bastias, MC, Hill, GA, Osteen, KG. Coculture of mouse embryos with cells isolated from the human ovarian follicle, oviduct, and uterine endometrium. Fertil Steril, 59(1), 138-42, 1993

Osteen, KG, Anderson, TL, Schwartz, K, Hargrove, JT, Gorstein, F. Distribution of tumor-associated glycoprotein-72 (TAG-72) expression throughout the normal female reproductive tract. Int J Gynecol Pathol, 11(3), 216-20, 1992

Hill, GA, Osteen, KG. The effect of insulin on in vitro progesterone production of human granulosa cells. Int J Fertil, 37(2), 93-8, 1992

Osteen, KG, Anderson, TL. Effect of estrogen on human endometrial epithelial cell growth and differentiation in vitro. Steroids, 56(5), 279-83, 1991

Segars, JH, Hill, GA, Bryan, SH, Herbert, CM, Osteen, KG, Rogers, BJ, Wentz, AC. The use of gonadotropin releasing hormone agonist (GnRHa) in good responders undergoing repeat in vitro fertilization/embryo transfer (IVF/ET). J In Vitro Fert Embryo Transf, 7(6), 327-31, 1990

Osteen, KG, Anderson, TL, Hargrove, JT, Hill, GA, Gorstein, F. Epithelial cells from normal human endometrium express a tumor-associated glycoprotein (TAG-72) epitope in vitro. Am J Obstet Gynecol, 163(2), 479-84, 1990

Herbert, CM, Hill, GA, Maxson, WS, Wentz, AC, Osteen, KG. Use of a sensitive urine pregnancy test before endometrial biopsies taken in the late luteal phase. Fertil Steril, 53(1), 162-4, 1990

Anderson, TL, Gorstein, F, Osteen, KG. Stromal-epithelial cell communication, growth factors, and tissue regulation. Lab Invest, 62(5), 519-21, 1990

Osteen, KG, Hill, GA, Hargrove, JT, Gorstein, F. Development of a method to isolate and culture highly purified populations of stromal and epithelial cells from human endometrial biopsy specimens. Fertil Steril, 52(6), 965-72, 1989

Hill, GA, Freeman, M, Bastias, MC, Rogers, BJ, Herbert, CM, Osteen, KG, Wentz, AC. The influence of oocyte maturity and embryo quality on pregnancy rate in a program for in vitro fertilization-embryo transfer. Fertil Steril, 52(5), 801-6, 1989

Blackburn, DG, Osteen, KG, Winfrey, VP, Hoffman, LH. Obplacental giant cells of the domestic rabbit: development, morphology, and intermediate filament composition. J Morphol, 202(2), 185-203, 1989

Segars, JH, Niblack, GD, Osteen, KG, Rogers, BJ, Wentz, AC. The human blastocyst produces a soluble factor(s) that interferes with lymphocyte proliferation. Fertil Steril, 52(3), 381-7, 1989

Aleshire, SL, Osteen, KG, Maxson, WS, Entman, SS, Bradley, CA, Parl, FF. Localization of transferrin and its receptor in ovarian follicular cells: morphologic studies in relation to follicular development. Fertil Steril, 51(3), 444-9, 1989

Hill, GA, Osteen, KG. Follicular fluid steroid content and in vitro steroid secretion by granulosa-lutein cells from individual follicles among different stimulation protocols for in vitro fertilization-embryo transfer. J In Vitro Fert Embryo Transf, 6(4), 201-6, 1989

Skinner, MK, Osteen, KG. Developmental and hormonal regulation of bovine granulosa cell function in the preovulatory follicle. Endocrinology, 123(3), 1668-75, 1988