scholarly journals Evaluation of human first trimester decidual and telomerase-transformed endometrial stromal cells as model systems of in vitro decidualization

2011 ◽  
Vol 9 (1) ◽  
pp. 155 ◽  
Author(s):  
Leila Saleh ◽  
Gerlinde R Otti ◽  
Christian Fiala ◽  
Jürgen Pollheimer ◽  
Martin Knöfler
2019 ◽  
Vol 101 (1) ◽  
pp. 138-147 ◽  
Author(s):  
Shijian Lv ◽  
Na Wang ◽  
Jin Ma ◽  
Wei-Ping Li ◽  
Zi-Jiang Chen ◽  
...  

Abstract Recurrent miscarriage (RM) is characterized by two or more consecutive losses of a clinically established intrauterine pregnancy at early gestation. To date, the etiology of RM remains poorly understood. Impaired decidualization is thought to predispose women to subsequent pregnancy failure. The transcriptional factor brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL1) controls circadian rhythms and regulates a very large diversity of physiological processes. BMAL1 is essential for fertility. Here, we investigated the expression and function of BMAL1 in human decidualization and its relation with RM. A total of 39 decidua samples were collected. We also examined human endometrial stromal cells (HESCs) and primary endometrial stromal cells (ESCs), and primary decidual stromal cells (DSCs) isolated from decidua of first-trimester pregnancies. Compared to normal pregnant women, the expression of BMAL1 was reduced in the decidual tissues from individuals with RM. After in vitro induction of decidualization, the transcription of BMAL1 in both HESCs and primary ESCs was increased. This is in line with the relatively higher expression of BMAL1 in DSCs than in ESCs. Silencing of BMAL1 resulted in impaired decidualization. Moreover, levels of tissue inhibitors of metalloproteinases (TIMPs) increased significantly upon decidualization. Further experiments demonstrated that BMAL1 silencing curtails the ability of DSCs to restrict excessive trophoblast invasion via downregulation of TIMP3. Our study demonstrates a functional role for BMAL1 during decidualization: the downregulation of BMAL1 in RM leads to impaired decidualization and aberrant trophoblast invasion by regulating TIMP3 and consequently predisposing individuals for RM.


2003 ◽  
Vol 88 (5) ◽  
pp. 2335-2340 ◽  
Author(s):  
Keisuke Tanaka ◽  
Hiroyuki Minoura ◽  
Tetsuya Isobe ◽  
Hitoshi Yonaha ◽  
Hiroaki Kawato ◽  
...  

Successful implantation involves a complex interaction between the endometrium and the embryo. It is well known that several neuropeptides are expressed in the endometrium and placenta during embryonal implantation, suggesting an important role as chemical mediators of the feto-maternal relationship. Ghrelin has recently been identified as the endogenous ligand for the GH secretagogue receptor. Ghrelin is a peptide hormone with many physiological functions, and its expression in the human placenta has been reported. To investigate the involvement of ghrelin in embryonal implantation, we assessed the spatio-temporal expression pattern of ghrelin and its receptor in the human endometrium and placenta through the normal menstrual cycle and in early pregnancy. We also examined the effect of ghrelin on the decidualization of endometrial stromal cells (ESC). Weak expression of ghrelin mRNA was detected in the nonpregnant endometrium, and it was dramatically increased in the decidualized endometrium. A GH secretagogue receptor mRNA was detected in the endometrium throughout the normal menstrual cycle and in early pregnancy, but not in the first trimester placenta. Immunohistochemical analysis using an antighrelin antibody revealed strong signals in decidual cells and extravillous trophoblast cells. Coculture with first trimester placenta up-regulated ghrelin mRNA expression by primary cultured ESC, although sex steroids and 8-bromo-cAMP had no effect. In addition, ghrelin enhanced the decidualization of ESC induced by 8-bromo-cAMP (8-Br-cAMP) in vitro. Thus, ghrelin is a novel paracrine/autocrine factor that is involved in cross-talk between the endometrium and embryo during embryonal implantation.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ryo Yokomizo ◽  
Yukiko Fujiki ◽  
Harue Kishigami ◽  
Hiroshi Kishi ◽  
Tohru Kiyono ◽  
...  

Abstract Background Thin endometrium adversely affects reproductive success rates with fertility treatment. Autologous transplantation of exogenously prepared endometrium can be a promising therapeutic option for thin endometrium; however, endometrial epithelial cells have limited expansion potential, which needs to be overcome in order to make regenerative medicine a therapeutic strategy for refractory thin endometrium. Here, we aimed to perform long-term culture of endometrial epithelial cells in vitro. Methods We prepared primary human endometrial epithelial cells and endometrial stromal cells and investigated whether endometrial stromal cells and human embryonic stem cell-derived feeder cells could support proliferation of endometrial epithelial cells. We also investigated whether three-dimensional culture can be achieved using thawed endometrial epithelial cells and endometrial stromal cells. Results Co-cultivation with the feeder cells dramatically increased the proliferation rate of the endometrial epithelial cells. We serially passaged the endometrial epithelial cells on mouse embryonic fibroblasts up to passage 6 for 4 months. Among the human-derived feeder cells, endometrial stromal cells exhibited the best feeder activity for proliferation of the endometrial epithelial cells. We continued to propagate the endometrial epithelial cells on endometrial stromal cells up to passage 5 for 81 days. Furthermore, endometrial epithelium and stroma, after the freeze-thaw procedure and sequential culture, were able to establish an endometrial three-dimensional model. Conclusions We herein established a model of in vitro cultured endometrium as a potential therapeutic option for refractory thin endometrium. The three-dimensional culture model with endometrial epithelial and stromal cell orchestration via cytokines, membrane-bound molecules, extracellular matrices, and gap junction will provide a new framework for exploring the mechanisms underlying the phenomenon of implantation. Additionally, modified embryo culture, so-called “in vitro implantation”, will be possible therapeutic approaches in fertility treatment.


2001 ◽  
Vol 16 (5) ◽  
pp. 836-845 ◽  
Author(s):  
Julia T. Arnold ◽  
David G. Kaufman ◽  
Markku Seppälä ◽  
Bruce A. Lessey

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