Skip to main content
Erschienen in: Archives of Gynecology and Obstetrics 2/2019

19.12.2018 | Gynecologic Endocrinology and Reproductive Medicine

Low-dose mifepristone increased angiogenesis in a manner involving AQP1

verfasst von: Feng Zhou, Zhida Qian, Lili Huang

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To investigate the molecular mechanisms governing aquaporin-1 (AQP1)-mediated, mifepristone-induced angiogenesis and improve the understanding of low-dose mifepristone serving as an anti-implantation contraceptive drug.

Methods

Human umbilical vein endothelial cells (HUVECs) were used to explore the effects of different concentrations of mifepristone (0, 65, and 200 nmol/L) on the activity of angiogenesis. Forty-five pregnant mice during the “window of implantation” were treated with different concentrations of mifepristone. HUVECs’ proliferation was examined using a methyl thiazolyl tetrazolium (MTT) assay. The microvessel density (MVD) and the expression of AQP1 in endometrium were determined with immunohistochemical methods.

Results

The MVD and the expression of AQP1 were significantly higher than controls. Mifepristone at 200 nmol/L significantly affected HUVECs’ proliferation during culture over 12 h, and pretreatment with AQP1-specific siRNA significantly inhibited the mifepristone-enhanced cell proliferation.

Conclusions

Low-dose mifepristone increased angiogenesis in a manner involving AQP1. This affords a new insight into the molecular mechanism underpinning the angiogenic effects of low-dose mifepristone.
Literatur
1.
Zurück zum Zitat Navot D, Bergh P (1991) Preparation of the human endometrium for implantation. Ann N Y Acad Sci 622:209–212CrossRef Navot D, Bergh P (1991) Preparation of the human endometrium for implantation. Ann N Y Acad Sci 622:209–212CrossRef
2.
Zurück zum Zitat Psychoyos A (1976) Hormonal control of uterine receptivity for nidation. J Reprod Fertil Suppl. 25:17–28 Psychoyos A (1976) Hormonal control of uterine receptivity for nidation. J Reprod Fertil Suppl. 25:17–28
3.
Zurück zum Zitat Smith SK (1998) Angiogenesis, vascular endothelial growth factor and the endometrium. Hum Reprod Update 4:509–519CrossRefPubMed Smith SK (1998) Angiogenesis, vascular endothelial growth factor and the endometrium. Hum Reprod Update 4:509–519CrossRefPubMed
4.
Zurück zum Zitat Sherer DM, Abulafia O (2001) Angiogenesis during implantation, and placental and early embryonic development. Placenta 22:1–13CrossRefPubMed Sherer DM, Abulafia O (2001) Angiogenesis during implantation, and placental and early embryonic development. Placenta 22:1–13CrossRefPubMed
5.
Zurück zum Zitat Nardo LG (2005) Vascular endothelial growth factor expression in the endometrium during the menstrual cycle, implantation window and early pregnancy. Curr Opin Obstet Gynecol 17:419–423CrossRefPubMed Nardo LG (2005) Vascular endothelial growth factor expression in the endometrium during the menstrual cycle, implantation window and early pregnancy. Curr Opin Obstet Gynecol 17:419–423CrossRefPubMed
6.
Zurück zum Zitat Demir R, Kayisli UA, Cayli S, Hupperzt B (2006) Sequential steps during vasculogenesis and angiogenesis in the very early human placenta. Placenta 27:535–539CrossRefPubMed Demir R, Kayisli UA, Cayli S, Hupperzt B (2006) Sequential steps during vasculogenesis and angiogenesis in the very early human placenta. Placenta 27:535–539CrossRefPubMed
7.
Zurück zum Zitat Ota H, Igarashi S, Tanaka T (1998) Morphometric evaluation of stromal vascularization in the endometrium in adenomyosis. Hum Reprod 13:715–719CrossRefPubMed Ota H, Igarashi S, Tanaka T (1998) Morphometric evaluation of stromal vascularization in the endometrium in adenomyosis. Hum Reprod 13:715–719CrossRefPubMed
8.
Zurück zum Zitat Carmeliet P (2005) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395CrossRef Carmeliet P (2005) Mechanisms of angiogenesis and arteriogenesis. Nat Med 6:389–395CrossRef
9.
Zurück zum Zitat Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364CrossRefPubMed Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364CrossRefPubMed
10.
Zurück zum Zitat Richard C, Gao J, Brown N, Reese J (2003) Aquaporin water channel genes are differentially expressed and regulated by ovarian steroids during the periimplantation period in the mouse. Endocrinology 144:1533–1541CrossRefPubMed Richard C, Gao J, Brown N, Reese J (2003) Aquaporin water channel genes are differentially expressed and regulated by ovarian steroids during the periimplantation period in the mouse. Endocrinology 144:1533–1541CrossRefPubMed
11.
Zurück zum Zitat Feng C, Sun CC, Wang TT, He RH, Sheng JZ, Huang HF (2008) Decreased expression of endometrial vessel AQP1 and endometrial epithelium AQP2 related to anovulatory uterine bleeding in premenopausal women. Menopause 15:648–654CrossRefPubMed Feng C, Sun CC, Wang TT, He RH, Sheng JZ, Huang HF (2008) Decreased expression of endometrial vessel AQP1 and endometrial epithelium AQP2 related to anovulatory uterine bleeding in premenopausal women. Menopause 15:648–654CrossRefPubMed
12.
Zurück zum Zitat Huebert RC, Jagavelu K, Hendrickson HI et al (2011) Aquaporin-1 promotes angiogenesis, fibrosis, and portal hypertension through mechanisms dependent on osmotically sensitive microRNAs. Am J Pathol 179:1851–1860CrossRefPubMedPubMedCentral Huebert RC, Jagavelu K, Hendrickson HI et al (2011) Aquaporin-1 promotes angiogenesis, fibrosis, and portal hypertension through mechanisms dependent on osmotically sensitive microRNAs. Am J Pathol 179:1851–1860CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Kapp N, Whyte P, Tang J, Jackson E, Brahmi D (2013) A review of evidence for safe abortion care. Contraception 88:350–363CrossRefPubMed Kapp N, Whyte P, Tang J, Jackson E, Brahmi D (2013) A review of evidence for safe abortion care. Contraception 88:350–363CrossRefPubMed
14.
Zurück zum Zitat Danielsson KG, Marions L, Bygdeman M (2003) Effects of mifepristone on endometrial receptivity. Steroids 68:1069–1075CrossRefPubMed Danielsson KG, Marions L, Bygdeman M (2003) Effects of mifepristone on endometrial receptivity. Steroids 68:1069–1075CrossRefPubMed
15.
Zurück zum Zitat Sarkar NN (2002) The potential of mifepristone (RU486) as a female contraceptive drug. Int J Clin Pract 56:140–144PubMed Sarkar NN (2002) The potential of mifepristone (RU486) as a female contraceptive drug. Int J Clin Pract 56:140–144PubMed
16.
Zurück zum Zitat Huang G, Chen L (2010) Recombinant human endostatin improves anti-tumor efficacy of paclitaxel by normalizing tumor vasculature in Lewis lung carcinoma. J Cancer Res Clin Oncol 136:1201–1211CrossRefPubMed Huang G, Chen L (2010) Recombinant human endostatin improves anti-tumor efficacy of paclitaxel by normalizing tumor vasculature in Lewis lung carcinoma. J Cancer Res Clin Oncol 136:1201–1211CrossRefPubMed
17.
Zurück zum Zitat Hildenbrand A, Stavreus-Evers A, Lalitkumar PGL, Nielsen S, Mints M, Gemzell-Danielsson K (2008) Aquaporin 1 is expressed in the human endometrium during normal cycle and increases after mifepristone treatment. Int J Mol Med 22:49–53PubMed Hildenbrand A, Stavreus-Evers A, Lalitkumar PGL, Nielsen S, Mints M, Gemzell-Danielsson K (2008) Aquaporin 1 is expressed in the human endometrium during normal cycle and increases after mifepristone treatment. Int J Mol Med 22:49–53PubMed
18.
Zurück zum Zitat Weichert H, Blechschmidt I, Schröder S, Ambrosius H (1991) The MTT-assay as a rapid test for cell proliferation and cell killing: application to human peripheral blood lymphocytes (PBL). Allerg Immunol 37(3–4):139–144 Weichert H, Blechschmidt I, Schröder S, Ambrosius H (1991) The MTT-assay as a rapid test for cell proliferation and cell killing: application to human peripheral blood lymphocytes (PBL). Allerg Immunol 37(3–4):139–144
19.
Zurück zum Zitat Saadoun S, Papadopoulos MC, Hara-Chikuma M, Verkman AS (2005) Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature 434:786–792CrossRefPubMed Saadoun S, Papadopoulos MC, Hara-Chikuma M, Verkman AS (2005) Impairment of angiogenesis and cell migration by targeted aquaporin-1 gene disruption. Nature 434:786–792CrossRefPubMed
20.
Zurück zum Zitat Huebert RC, Jagavelu K, Hendrickson HI, Vasdev MM, Arab JP, Splinter PL, Trussoni CE, Larusso NF, Shah VH (2011) Aquaporin-1 promotes angiogenesis, fibrosis, and portal hypertension through mechanisms dependent on osmotically sensitive microRNAs. Am J Pathol 179:1851–1860CrossRefPubMedPubMedCentral Huebert RC, Jagavelu K, Hendrickson HI, Vasdev MM, Arab JP, Splinter PL, Trussoni CE, Larusso NF, Shah VH (2011) Aquaporin-1 promotes angiogenesis, fibrosis, and portal hypertension through mechanisms dependent on osmotically sensitive microRNAs. Am J Pathol 179:1851–1860CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Zhao W, Shen H, Yuan F, Li G, Sun Y, Shi Z, Zhang Y, Wang Z (2009) Induction stage-dependent expression of vascular endothelial growth factor and aquaporin-1 in diethylstilbestrol-treated rat pituitary. Eur J Histochem 53:53–60CrossRefPubMed Zhao W, Shen H, Yuan F, Li G, Sun Y, Shi Z, Zhang Y, Wang Z (2009) Induction stage-dependent expression of vascular endothelial growth factor and aquaporin-1 in diethylstilbestrol-treated rat pituitary. Eur J Histochem 53:53–60CrossRefPubMed
22.
Zurück zum Zitat Smith SK (2001) Regulation of angiogenesis in the endometrium. Trends Endocrinol Metab 12(4):147–151CrossRefPubMed Smith SK (2001) Regulation of angiogenesis in the endometrium. Trends Endocrinol Metab 12(4):147–151CrossRefPubMed
23.
Zurück zum Zitat Au CL, Rogers PA (1993) Immunohistochemical staining of von Willebrand factor in human endometrium during normal menstrual cycle. Hum Reprod 8:17–23CrossRefPubMed Au CL, Rogers PA (1993) Immunohistochemical staining of von Willebrand factor in human endometrium during normal menstrual cycle. Hum Reprod 8:17–23CrossRefPubMed
24.
Zurück zum Zitat Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and etastasis-corelation in invasive breast carcinoma. N Engl J Med 324(1):1–8CrossRefPubMed Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and etastasis-corelation in invasive breast carcinoma. N Engl J Med 324(1):1–8CrossRefPubMed
25.
Zurück zum Zitat Choi WW, Lewis MM, Lawson D, Yin-Goen Q, Birdsong GG et al (2005) Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol 18:143–152CrossRef Choi WW, Lewis MM, Lawson D, Yin-Goen Q, Birdsong GG et al (2005) Angiogenic and lymphangiogenic microvessel density in breast carcinoma: correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol 18:143–152CrossRef
26.
Zurück zum Zitat Zhou F, Liang Y, Qian ZD, Zhuang YL, Chen YZ, Lv BJ, Zhou CY, Chen XD, Huang LL (2013) Low-dose mifepristone increases uterine expression of aquaporin 1/aquaporin 2 at the time of implantation. Contraception 87(6):844–849CrossRefPubMed Zhou F, Liang Y, Qian ZD, Zhuang YL, Chen YZ, Lv BJ, Zhou CY, Chen XD, Huang LL (2013) Low-dose mifepristone increases uterine expression of aquaporin 1/aquaporin 2 at the time of implantation. Contraception 87(6):844–849CrossRefPubMed
27.
Zurück zum Zitat Zou LB, Shi S, Zhang RJ, Wang TT, Tan YJ, Zhang D, Fei XY, Ding GL, Gao Q, Chen C, Hu XL, Huang HF, Sheng JZ (2013) Aquaporin-1 plays a crucial role in estrogen-induced tubulogenesis of vascular endothelial cells. J Clin Endocrinol Metab 98:E672–E682CrossRefPubMed Zou LB, Shi S, Zhang RJ, Wang TT, Tan YJ, Zhang D, Fei XY, Ding GL, Gao Q, Chen C, Hu XL, Huang HF, Sheng JZ (2013) Aquaporin-1 plays a crucial role in estrogen-induced tubulogenesis of vascular endothelial cells. J Clin Endocrinol Metab 98:E672–E682CrossRefPubMed
28.
Zurück zum Zitat Glasier AF, Wang H, Davie JE, Kelly RW, Critchley HOD (2002) Administration of an antiprogesterone up-regulates estrogen receptors in the endometrium of women using Norplant™: a pilot study. Fertil Steril 77:366–372CrossRefPubMed Glasier AF, Wang H, Davie JE, Kelly RW, Critchley HOD (2002) Administration of an antiprogesterone up-regulates estrogen receptors in the endometrium of women using Norplant™: a pilot study. Fertil Steril 77:366–372CrossRefPubMed
Metadaten
Titel
Low-dose mifepristone increased angiogenesis in a manner involving AQP1
verfasst von
Feng Zhou
Zhida Qian
Lili Huang
Publikationsdatum
19.12.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 2/2019
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-018-4989-9

Weitere Artikel der Ausgabe 2/2019

Archives of Gynecology and Obstetrics 2/2019 Zur Ausgabe

Hirsutismus bei PCOS: Laser- und Lichttherapien helfen

26.04.2024 Hirsutismus Nachrichten

Laser- und Lichtbehandlungen können bei Frauen mit polyzystischem Ovarialsyndrom (PCOS) den übermäßigen Haarwuchs verringern und das Wohlbefinden verbessern – bei alleiniger Anwendung oder in Kombination mit Medikamenten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bislang gibt es kein Medikament zur Prävention von Wochenbettdepressionen. Das Injektionsanästhetikum Esketamin könnte womöglich diese Lücke füllen.

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

22.04.2024 DGIM 2024 Kongressbericht

Durch die Häufung nach der COVID-19-Pandemie sind Infektionen mit dem Respiratorischen Synzytial-Virus (RSV) in den Fokus gerückt. Fachgesellschaften empfehlen eine Impfung inzwischen nicht nur für Säuglinge und Kleinkinder.

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.