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Gynecologic Endocrinology and Fertility Disorders

Scientific work of our group

The womb is lined with a 1 cm layer of tissue, the endometrium, which is shed every 4 weeks as part of menstrual bleeding. If a pregnancy occurs, the embryo implants into the endometrium around 5 days after ovulation and forms the placenta. This implantation phase is extremely sensitive and may be subject to various disorders leading to the embryo being rejected.

 

As an endometrial implantation disorder could be responsible for infertility and the limited success rate of IVF and ICSI treatments, our working group systematically investigates the function of the endometrium and its regulatory disorders using examination techniques from the fields of molecular biology and protein biochemistry.

 

Our examinations focus on the different stages of endometrial implantation:

 

     

  1. On the basis of tissue samples and cell cultures, the production and regulation of various endometrial factors, such as pro-inflammatory cytokines, are investigated which are likely to play a role in the endometrial preparation of implantation.

  2. Furthermore, adhesion proteins such as integrins, osteopontin, galectins etc. which regulate the first phase of implantation, the attachment of the embryo to the endometrium, are analysed.

  3. The interaction of the embryo with the mother's endometrium as implantation progresses is imitated and analysed in a cell culture model.

  4. We look at how endometrial cells are supplied with glucose as an energy carrier in order to gain insights into the metabolic processes accompanying the endometrial tissue change during implantation.

  5. Endometrial biopsy samples of patients with implantation failure or repeated miscarriages are taken to characterise various functional markers in order to analyse endometrial function disorders in the late phase of implantation.

  6.  

 

These investigations have already expanded our insight into endometrial regulation to such an extent that we have developed an endometrial stimulation therapy with seminal fluid in the cell culture model. In the infertility clinic, this therapy for endometrial function disorders is now offered as part of IVF or ICSI treatment.

 

Main original publications of the last years about

„Endometrium & Implantation“

 

von Wolff, M., Strowitzki,T., Stieger, S. Becker, V., Zepf, C., Tabibzadeh, S., Thaler, C.J. Osteopontin and its receptor b3-integrin - mRNA and protein expression in human endometrium. Fertil. Steril. (2001) 76:775-781.

 

Strowitzki, T., Capp, E., von Wolff, M., Müller-Höcker, J. Expression of glucose transporter 1 in human endometrial and decidual tissue. Gynecol. Endocrinol. (2001) 15: 219-224.

 

von Wolff, M., Thaler, C.J., Zepf, C., Becker, V., Beier, H.M., Stowitzki, T. Endometrial expression and secretion of Interleukin 6 (IL-6) throughout the menstrual cycle. Gynecol. Endocrinol. (2002) 16: 121-129.

 

von Wolff, M., Stieger, S., Lumpp, K., Bückung, J., Thaler, C.J., Stowitzki, T. Endometrial Interleukin 6 (IL-6) is not directly regulated by female steroid hormones but by pro-inflammatory cytokines and hypoxia in vitro. Mol Hum Reprod. (2002) 8:1096-1102.

 

Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA, Giudice LC. Global gene profiling in human endometrium during the window of implantation. Endocrinology. (2002) 143: 2119-2138.

 

von Wolff, M., Walter S., Jauckus J., Kern A., Hahn U, Steldinger R., Strowitzki T. Glucose transporter proteins (GLUT) in human endometrium – expression, regulation and function throughout the menstrual cycle and in early pregnancy. J. Clin. Endocrinol. Metab. (2003) 88: 3885-3892.

 

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. (2003) 44: 2870-2881.

 

Gutsche S. & von Wolff M., Strowitzki T., Thaler C.J. Seminal plasma induces mRNA expression of IL-1b, IL-6 and LIF in endometrial epithelial cells vitro. Mol. Hum. Reprod., (2003) 9: 785-91.

 

Tulac S, Nayak NR, Kao LC, Van Waes M, Huang J, Lobo S, Germeyer A, Lessey BA, Taylor RN, Suchanek E, Giudice LC.Identification, characterization, and regulation of the canonical Wnt signaling pathway in human endometrium. J Clin Endocrinol Metab. (2003) 88:3860-6.

 

von Wolff M., Bohlmann M., Fiedler C., Ursel S., Strowitzki T. Osteopontin is upregulated in decidual stromal cells. Fertil Steril. (2004) 81 Suppl 1:741-748.

 

Germeyer A, Hamilton AE, Laughlin LS, Lasley BL, Brenner RM, Giudice LC, Nayak NR. Cellular expression and hormonal regulation of neuropilin-1 and -2 mRNA in the human and rhesus macaque endometrium. J Clin Endocrinol Metab. 2005 Mar;90(3):1783-90. Epub 2004 Dec 21.

 

Lobo SC, Huang ST, Germeyer A, Dosiou C, Vo KC, Tulac S, Nayak NR, Giudice LC. The immune environment in human endometrium during the window of implantation. Am J Reprod Immunol. (2004) 52:244-51.

 

von Wolff M. , Wang X., Gabius H.-J., Strowitzki T. Galectin fingerprinting in human endometrium and decidua during the menstrual cycle and in early gestation. Mol Hum Reprod, (2005) 11:189-194.

 

Popovici RM, Krause MS, Germeyer A, Strowitzki T, von Wolff M. Galectin-9: a new endometrial epithelial marker for the mid- and late-secretory and decidual phases in humans. J Clin Endocrinol Metab. 2005 Nov;90(11):6170-6. Epub 2005 Aug 16.

 

Strowitzki T, Germeyer A, Popovici R and von Wolff M: The human endometrium as a fertility-determining factor. Review. Hum Reprod Update. 2006 Sep-Oct;12(5):617-30. Epub 2006 Jul 10.

 

Popovici RM, Betzler NK, Krause MS, Luo M, Jauckus J, Germeyer A, Bloethner S, Schlotterer A, Kumar R, Strowitzki T, von Wolff M: Gene expression profiling of human endometrial-trophoblast interaction in a coculture model. Endocrinology. 2006 Dec;147(12):5662-75. Epub 2006 Aug 31.

 

Germeyer A, Klinkert MS, Huppertz AG, Clausmeyer S, Popovici RM, Strowitzki T, von Wolff M: Expression of syndecans, cell-cell-interaction regulating heparan sulfate proteoglycans, within the human endometrium and their regulation throughout the menstrual cycle. Fertil Steril. 2007 Mar;87(3):657-63. Epub 2006 Nov 21.

 

Popovici RM, Krause MS, Jauckus J, Germeyer A, Brum IS, Garlanda C, Strowitzki T, von Wolff M. The long pentraxin PTX3 in human endometrium: regulation by steroids and trophoblast products. Endocrinology. 2008 Mar;149(3):1136-43. Epub 2007 Nov 29.

 

Germeyer A, Sharkey AM, Prasadajudio M, Sherwin R, Moffett A, Bieback K, Clausmeyer S, Leanne M, Popovici RM, Hess AP, Strowitzki T, von Wolff M. Paracrine effects of uterine leukocytes on gene expression of human uterine stromal fibroblasts. Mol Hum Reprod. 2009 Jan;15(1):39-48. Epub 2008 Dec 16.

 

von Wolff M, Rösner S, Thöne C, Pinheiro RM, Jauckus J, Bruckner T, Biolchi V, Alia A, Strowitzki T. Intravaginal and intracervical application of seminal plasma in in vitro fertilization or intracytoplasmic sperm injection treatment cycles--a double-blind, placebo-controlled, randomized pilot study. Fertil Steril. 2009 Jan;91(1):167-72. Epub 2008 Feb 4.

 

Von Wolff M, Germeyer A, Strowitzki T. German. Implantation –Physiologie, Pathologie und therapeutische Optionen bei Implantationsstörungen. „[Implantation: physiology, pathology and therapeutic options in disorders of implantation]“ Gynakol Geburtshilfliche Rundsch. 2009;49(2):69-79. Epub 2009 Mar 25. Review.

 

Strowitzki T, Germeyer A. "Fertilität und Krebs – ein neues Aufgabengebiet für die Reproduktionsmedizin?" J Gynäkol Endokrinol 2009; 19 (4): 30-33.

 

Fitzgerald JS, Germeyer A, Huppertz B, Jeschke U, Knöfler M, Moser G, Scholz C, Sonderegger S, Toth B, Markert UR. [Epub ahead of print]. Governing the invasive trophoblast: Current aspects on intra- and extracellular regulation. Review. Am J Reprod Immunol. 2010 Mar 17.

 

Germeyer A, von Wolff M, Jauckus J, Strowitzki T, Sharma T and Grazul-Bilska A. Changes in cell proliferation, but not in vascularisation are characteristic for human endometrium in different reproductive failures – a pilot study. Reprod Biol Endocrinol. 2010 Jun 21; 8(1):67.

 

Germeyer A, Senghaas A, Strowitzki T, von Wolff M. Besteht ein Effekt des Immuntherapeutikums LeukoNorm® auf die Steigerung der Implantationsfähigkeit im humanen Endometrium? GebFra Juni 2010 70. Jahrgang; 488-493.

 

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