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Expressions of Ninjurin-1 in endometriosis and adenomyosis
Abstracts / Journal of Reproductive Immunology 115 (2016) 71–90
while proliferation decreased. Overexpression of miR-520d-3p resulted in increased proliferation in HTR-8/SVneo cells. Conclusion: C19MC microRNAs may be involved in controlling proliferation and migration of trophoblast cells and their dysregulation may be associated with pregnancy diseases such as PE. http://dx.doi.org/10.1016/j.jri.2016.04.238 P2-20 Expression of prorenin (REN) and angiotensin 1-7 receptor (MAS1) mRNA and in local endometriosis lesions Takahiro Nakajima, Fumihisa Chishima, Takehiro Nakao, Chuyu Hayashi, Yoichi Aoki, Motomi Yamazaki, Go Ichikawa, Kenji Sugita, Tatsuo Yamamoto Department of Obstetrics and Gynecology, Nihon University School of Medicine, Japan Introduction: Renin–angiotensin system is involved in blood pressure regulation and water balance. Macrophages secrete inflammatory cytokines and prostaglandins in response to stimulation of receptors, as TLR4 and angiotensin (Ang) receptors. In human endometrium including stromal cells, receptors of the AT1/AT2 types have been detected. Binding of prorenin (REN) to ATP6AP2 activates it and catalyse the formation of Ang I from angiotensinogen. Ang-(1-7) is produced by cleavage of Ang II by angiotensin-converting-enzyme type 2. Ang-(1-7) acts through binding to MAS1. We investigated into the expression of REN and MAS1 in local lesions of endometriosis. Methods of study: Endometriosis samples were obtained from patients of endometrial cyst. Endometrial tissues were obtained from patients undergoing surgery for benign gynecological conditions. Informed consents were obtained from all the patients participating in this study. The expression of MAS1, REN, AT1/AT2 receptors mRNA was examined by quantitative real-time PCR. Results: REN and MAS1 mRNA expressions were detected in all samples. No significant differences were observed in REN and MAS1 mRNA of the eutopic endometria at any phase in controls. Higher REN and MAS1 mRNA expressions were observed in endometriotic lesion. There was a relationship between expression of MAS1 and AT1 receptor mRNA in endometriosis samples. Conclusion: RAS may have an important role in the pathogenesis of endometriosis via function of macrophages. http://dx.doi.org/10.1016/j.jri.2016.04.239 P2-21 Expression of thyroid hormone receptors (THR) is regulated by the progesterone receptor system in first trimester placental tissue and in BeWo cells in vitro Aurelia Vattai, Brigitte Ziegelmüller, Bernd Kost, Christina Kuhn, Simone Hofmann, Birgit Bayer, Katja Anslinger, Sven Mahner, Bettina Toth, Nina Ditsch, Udo Jeschke Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University Hospital, Munich, Germany Background: Thyroid hormones are essential for the maintenance of pregnancy and a deficiency in maternal thyroid hormones has been associated with early pregnancy losses. Aim of this study
77
was a systematic investigation of the influence of mifepristone (RU 486) on the expression of the thyroid hormone receptor (THR) isoforms THR␣1, THR␣2, THR1 and THR2 in placental tissue and in trophoblast tumour cells. Methods: Samples of placental tissue were obtained from patients with mifepristone induced legal termination of pregnancy (n = 13) or mechanically induced legal termination of pregnancy (n = 20) (pregnancy weeks 4-13). Immunohistochemistry and real time RT-PCR (TaqMan) were applied for the investigation. Results: Nuclear expression of THR␣1, THR␣2 and THR1 is downregulated on protein level in RU 486 treated villous trophoblast tissue compared to untreated villous trophoblasts. In decidual tissue, only THR␣1 expression is significantly reduced through RU 486. The majority of cells expressing THRs in the decidua are decidual stromal cells. Progesterone significantly reduced THRA but not THRB expression in trophoblast tumour cells. Conclusion: Downregulation of THR␣1, THR␣2 and THR1 and THRA in placental tissue through mifepristone may be induced through the inhibition of the progesterone receptor. This assumption is supported by the finding that stimulation of the progesterone receptor by progesterone itself up-regulates THRA in trophoblast cells in vitro. http://dx.doi.org/10.1016/j.jri.2016.04.240 P2-22 Expressions of Ninjurin-1 in endometriosis and adenomyosis Mariko Miyashita, Kaori Koga, Arisa Takeuchi, Tomoko Makabe, Fusako Sue, Osamu Yoshino, Tomoyuki Fujii, Yutaka Osuga Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, Japan Objectives: Endometriosis causes abdominal pain but the mechanism is unknown. Ninjurin-1 (Ninj1) is a protein produced on nerve injury and responsible for the nerve regeneration. The aim of this study was to assess the expression of Ninj1 in tissues of endometrioma (E), peritoneal endometriosis (P) and adenomyosis (A), and its regulator in endometriotic stromal cells (ESC). Methods: E were gained from patients with or without dysmenorrhea. P and A were gained from patients with dysmenorrhea. Ninj1 protein expression was determined by immunostaining. Localization of nerves and endometriotic stroma in lesions was assessed by immunostaining of PGP-9.5 and CD-10, respectively. ESC were isolated from E and cultured with/without IL-1 (5 ng/ml). Ninj1 mRNA expression was measured by RT-PCR. Results: In E, positive staining for Ninj1 was observed in both epithelial and stromal area. Part of Ninj1 positive area was also positive for PGP-9.5 and CD-10. In P and A, positive staining for Ninj1 was observed in both epithelium and stroma, and part of them were positive for PGP-9.5. IL-1 induced Ninj1 mRNA expression in ESC, approximately 10 times at 3 h (P < 0.05). Conclusion: Ninj1 is expressed in endometriosis and adenomyosis, and the expression seemed to be enhanced by inflammation. These findings indicate that inflammation in endometriosis induces Ninj1, and thus causes local nerve regeneration and may contribute to the disease-associated pain. http://dx.doi.org/10.1016/j.jri.2016.04.241
while proliferation decreased. Overexpression of miR-520d-3p resulted in increased proliferation in HTR-8/SVneo cells. Conclusion: C19MC microRNAs may be involved in controlling proliferation and migration of trophoblast cells and their dysregulation may be associated with pregnancy diseases such as PE. http://dx.doi.org/10.1016/j.jri.2016.04.238 P2-20 Expression of prorenin (REN) and angiotensin 1-7 receptor (MAS1) mRNA and in local endometriosis lesions Takahiro Nakajima, Fumihisa Chishima, Takehiro Nakao, Chuyu Hayashi, Yoichi Aoki, Motomi Yamazaki, Go Ichikawa, Kenji Sugita, Tatsuo Yamamoto Department of Obstetrics and Gynecology, Nihon University School of Medicine, Japan Introduction: Renin–angiotensin system is involved in blood pressure regulation and water balance. Macrophages secrete inflammatory cytokines and prostaglandins in response to stimulation of receptors, as TLR4 and angiotensin (Ang) receptors. In human endometrium including stromal cells, receptors of the AT1/AT2 types have been detected. Binding of prorenin (REN) to ATP6AP2 activates it and catalyse the formation of Ang I from angiotensinogen. Ang-(1-7) is produced by cleavage of Ang II by angiotensin-converting-enzyme type 2. Ang-(1-7) acts through binding to MAS1. We investigated into the expression of REN and MAS1 in local lesions of endometriosis. Methods of study: Endometriosis samples were obtained from patients of endometrial cyst. Endometrial tissues were obtained from patients undergoing surgery for benign gynecological conditions. Informed consents were obtained from all the patients participating in this study. The expression of MAS1, REN, AT1/AT2 receptors mRNA was examined by quantitative real-time PCR. Results: REN and MAS1 mRNA expressions were detected in all samples. No significant differences were observed in REN and MAS1 mRNA of the eutopic endometria at any phase in controls. Higher REN and MAS1 mRNA expressions were observed in endometriotic lesion. There was a relationship between expression of MAS1 and AT1 receptor mRNA in endometriosis samples. Conclusion: RAS may have an important role in the pathogenesis of endometriosis via function of macrophages. http://dx.doi.org/10.1016/j.jri.2016.04.239 P2-21 Expression of thyroid hormone receptors (THR) is regulated by the progesterone receptor system in first trimester placental tissue and in BeWo cells in vitro Aurelia Vattai, Brigitte Ziegelmüller, Bernd Kost, Christina Kuhn, Simone Hofmann, Birgit Bayer, Katja Anslinger, Sven Mahner, Bettina Toth, Nina Ditsch, Udo Jeschke Department of Gynaecology and Obstetrics, Ludwig-Maximilians-University Hospital, Munich, Germany Background: Thyroid hormones are essential for the maintenance of pregnancy and a deficiency in maternal thyroid hormones has been associated with early pregnancy losses. Aim of this study
77
was a systematic investigation of the influence of mifepristone (RU 486) on the expression of the thyroid hormone receptor (THR) isoforms THR␣1, THR␣2, THR1 and THR2 in placental tissue and in trophoblast tumour cells. Methods: Samples of placental tissue were obtained from patients with mifepristone induced legal termination of pregnancy (n = 13) or mechanically induced legal termination of pregnancy (n = 20) (pregnancy weeks 4-13). Immunohistochemistry and real time RT-PCR (TaqMan) were applied for the investigation. Results: Nuclear expression of THR␣1, THR␣2 and THR1 is downregulated on protein level in RU 486 treated villous trophoblast tissue compared to untreated villous trophoblasts. In decidual tissue, only THR␣1 expression is significantly reduced through RU 486. The majority of cells expressing THRs in the decidua are decidual stromal cells. Progesterone significantly reduced THRA but not THRB expression in trophoblast tumour cells. Conclusion: Downregulation of THR␣1, THR␣2 and THR1 and THRA in placental tissue through mifepristone may be induced through the inhibition of the progesterone receptor. This assumption is supported by the finding that stimulation of the progesterone receptor by progesterone itself up-regulates THRA in trophoblast cells in vitro. http://dx.doi.org/10.1016/j.jri.2016.04.240 P2-22 Expressions of Ninjurin-1 in endometriosis and adenomyosis Mariko Miyashita, Kaori Koga, Arisa Takeuchi, Tomoko Makabe, Fusako Sue, Osamu Yoshino, Tomoyuki Fujii, Yutaka Osuga Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, Japan Objectives: Endometriosis causes abdominal pain but the mechanism is unknown. Ninjurin-1 (Ninj1) is a protein produced on nerve injury and responsible for the nerve regeneration. The aim of this study was to assess the expression of Ninj1 in tissues of endometrioma (E), peritoneal endometriosis (P) and adenomyosis (A), and its regulator in endometriotic stromal cells (ESC). Methods: E were gained from patients with or without dysmenorrhea. P and A were gained from patients with dysmenorrhea. Ninj1 protein expression was determined by immunostaining. Localization of nerves and endometriotic stroma in lesions was assessed by immunostaining of PGP-9.5 and CD-10, respectively. ESC were isolated from E and cultured with/without IL-1 (5 ng/ml). Ninj1 mRNA expression was measured by RT-PCR. Results: In E, positive staining for Ninj1 was observed in both epithelial and stromal area. Part of Ninj1 positive area was also positive for PGP-9.5 and CD-10. In P and A, positive staining for Ninj1 was observed in both epithelium and stroma, and part of them were positive for PGP-9.5. IL-1 induced Ninj1 mRNA expression in ESC, approximately 10 times at 3 h (P < 0.05). Conclusion: Ninj1 is expressed in endometriosis and adenomyosis, and the expression seemed to be enhanced by inflammation. These findings indicate that inflammation in endometriosis induces Ninj1, and thus causes local nerve regeneration and may contribute to the disease-associated pain. http://dx.doi.org/10.1016/j.jri.2016.04.241