My research goal is to unravel root and proximal mechanisms by which endometriosis decreases fecundity such that the outcome of this research will have a significant impact on development of novel, targeted approaches for restoration of fertility in endometriosis and further to provide the first evidence to explain the familial nature of endometriosis, which may be via epigenetic or other non-genetic mechanisms.
In the early 1990s, my research made the pioneering discovery that endometriotic lesions synthesize and secrete tissue inhibitor of metalloproteinase 1 (TIMP1) into the peritoneal fluid, first in a well-established endometriosis model in the rat (Endo) and later that same year in women with endometriosis. We have further discovered that endometriosis disrupts with fertility through a negative impact on ovarian dynamics, oocyte quality and pre-implantation embryo development and increased spontaneous pregnancy.
These anomalies clearly mimic those found in subfertile women with endometriosis. Profoundly, these breakthrough findings provided the first insights into mechanisms causing subfertility in endometriosis. Our whole genome wide microarray studies of 8-cell stage embryos from endometriosis mothers, but not control mothers, demonstrate altered expression of several specific gene pathways negatively effecting embryo development. Some of the important pathways identified in the array include imprinting, apoptosis and autophagy. Intriguingly, we found altered gene expression in three subsequent generations of 8-cell embryos (F1, fetal exposure; F2 (fetal germ cell exposure) and F3 (no direct exposure to endometriosis). Collectively these data support the theory that endometriotic lesions in the peritoneal cavity are associated with subfertility in subsequent generations and provide the first evidence to explain the familial nature of endometriosis, for which to date no consistent genetic link has been identified.
We are uniquely poised to continue exploring and unraveling mechanisms whereby endometriosis deteriorates fertility and across generations.
- Endometrial anomalies
- Ovarian Dysfunction
- Embryo development
Education & Training
The University of Kentucky, Lexington
The University of Tennessee, Knoxville
- Birt JA, Nabli H, Stilley JA, Windham EA, Frazier SR, Sharpe-Timms KL. Elevated peritoneal fluid TNF-α incites ovarian early growth response factor 1 expression and downstream protease mediators: a correlation with ovulatory dysfunction in endometriosis. Reprod Sci. 2013 May;20(5):514-23. doi: 10.1177/1933719113477479. Epub 2013 Feb 20. PubMed PMID: 23427178.
K.L. Sharpe-Timms is a member of the World Endometriosis Society (WES), serving on their Board of Directors. She is an active contributor in the World Endometriosis Research Foundation (WERF) EPHect Working Group. She contributed to concept development, writing and reviewing manuscripts 57, 59 – 64, 66.
- Johnson NP, Hummelshoj L, the World Endometriosis Society Montpellier Consortium (Abrao MS, Adamson GD, Allaire C, Amelung V, Andersson E, Becker C, Birna Árdal KB, Bush D, de Bie B, Chwalisz K, Critchley H, D’Hooghe T, Dunselman G, Evers JLH, Farquhar C, Faustmann T, Forman A, Fourquet J, Fraser I, Giudice L, Gordts S, Guidone H, Guo SW, Healy D, Hedon B, Hulkkonen J, Hull L, Hummelshoj L, Johnson NP, Just M, Kiesel L, Lam A, Lynam C, Mettler L, Miller C, North H, Pai R, Petta C, Prentice L, Reilly S, Reis F, Rolla E, Rombauts L, Schweppe KW, Seckin T, Sharpe-Timms KL, Shepperson Mills D, Singh S, Soriano D, Stafford-Bell M, Stratton P, Taylor R, Tsaltas J, Veit J, Vercellini P). Consensus on current management of endometriosis. Hum Reprod 2013; Hum Reprod. 2013 Jun;28(6):1552-68. doi: 10.1093/humrep/det050. Epub 2013 Mar 25. PubMed PMID: 23528916.
- Birt JA, Taylor KH, Davis JW, Sharpe-Timms KL. Developmental exposure of fetal ovaries and fetal germ cells to endometriosis in an endometriosis model causes differential gene expression in the preimplantation embryos of the first-generation and second-generation embryos. Fertil Steril. 2013 Nov;100(5):1436-43. Epub 2013 Aug 15. PMID: 23954358; PMCID: PMC3847911.
The proceeding article was recommended by Faculty of 1000 PRIME: F1000Prime Recommendations, Dissents and Comments for [Birt JA et al., Fertil Steril 2013]. In F1000Prime, 11 Sep 2013; F1000Prime.com/718077638.
- Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, Bush D, Kiesel L, Tamimi R, Sharpe-Timms KL, Rombauts L, and Giudice LC for the World Endometriosis Society Sao Paulo Consortium. World Endometriosis Society Consensus on current management of endometriosis. Hum Reprod. 2013 Jun;28(6):1552-68. doi: 10.1093/humrep/det050. PubMed PMID: 23528916.
- Becker CM, Laufer MR, Stratton P, Hummelshoj L, Missmer SA, Zondervan KT, Adamson GD; WERF EPHect Working Group. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: I. Surgical phenotype data collection in endometriosis research. Fertil Steril. 2014 Aug 20. pii:S0015-0282(14)01336-3. doi: 10.1016/j.fertnstert.2014.07.709. [Epub ahead of print] Review. PubMed PMID: 25150390
- Vitonis AF, Vincent K, Rahmioglu N, Fassbender A, Buck Louis GM, Hummelshoj L, Giudice LC, Stratton P, Adamson GD, Becker CM, Zondervan KT, Missmer SA; WERF EPHect Working Group. World Endometriosis Research Foundation Endometriosis phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research. Fertil Steril. 2014 Sep 18. pii: S0015-0282(14)01885-8. doi: 10.1016/j.fertnstert.2014.07.1244. [Epub ahead of print] Review. PubMed PMID: 25256930.
- Rahmioglu N, Fassbender A, Vitonis AF, Tworoger SS, Hummelshoj L, D'Hooghe TM, Adamson GD, Giudice LC, Becker CM, Zondervan KT, Missmer SA; for the WERF EPHect Working Group. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research. Fertil Steril. 2014 Sep 17. pii: S0015-0282(14)01835-4. doi: 10.1016/j.fertnstert.2014.07.1208. [Epub ahead of print] Review. PubMed PMID: 25256929.
- Fassbender A, Rahmioglu N, Vitonis AF, Viganò P, Giudice LC, D'Hooghe TM, Hummelshoj L, Adamson GD, Becker CM, Missmer SA, Zondervan KT; for the WERF EPHect Working Group. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: IV. Tissue Collection, processing, and storage in endometriosis research. Fertil Steril. 2014 Sep 17. pii:S0015-0282(14)01836-6. doi: 10.1016/j.fertnstert.2014.07.1209. [Epub ahead of print] Review. PubMed PMID: 25256928.
- Casper RF. Introduction: new tools for enhancing collaborative endometriosis research. Fertil Steril. 2014 Nov;102(5):1211-2. PubMed PMID: 25154678.This issue of Fertility and Sterility contains four articles by the World Endometriosis Research Foundation whose present objective is global standardization of the collection of phenotypic data and biological samples, designated as the Endometriosis Phenome and Biobanking Harmonisation Project. The aim is to facilitate large-scale international, multicenter trials that are robust, and will result in biomarker and treatment targets to advance research in endometriosis.
- Hennings JM, Zimmer RL, Nabli H, Davis JW, Sutovsky P, Sutovsky M, Sharpe-Timms KL. Improved Murine Blastocyst Quality and Development in a Single Culture Medium Compared to Sequential Culture Media. Reprod Sci. 2016 Mar;23(3):310-7. Epub 2015 Dec 13. PMID: 26668049.
- Johnson NP, Hummelshoj L, Adamson GD, Keckstein J, Taylor HS, Abrao MS, Bush D, Kiesel L, Tamimi R, Sharpe-Timms KL, Rombauts L, Giudice LC, for the World Endometriosis Society Sao Paulo Consortium. World Endometriosis Society consensus on the classification of endometriosis. Hum. Reprod. Advance Access published December 5, 2016. doi:10.1093/humrep/dew293.