Expression and regulation of vasoactive substances, sex steroids and their receptors in placenta during normal pregnancy and preeclampsia
Author: Nasiell, Josefine
Date: 2002-05-03
Location: Föreläsningssal R64, Huddinge Universitetssjukhus
Time: 9.15
Department: Institutionen för klinisk vetenskap / Department of Clinical Sciences
View/ Open:
Thesis (411.7Kb)
Abstract
Despite intense studies preeclampsia remains enigmatic and a major cause of maternal and fetal morbidity and mortality. It is now widely accepted that the placenta has a central role in preeclampsia; delivery of the placenta is the only known cure. Its manifestations are considered secondary to inadequate trophoblast invasion of the uterine spiral arteries, which leads to placenta] ischemia and further to the devastating multisystem disorder of the mother and often the fetus. The syndrome is characterised by increased vasoconstriction and endothelial dysfunction.
Several biochemical changes in the placenta are evident. The nitric oxide (NO) system as well as the sex steroid hormones, estrogen and progesterone have been implicated in the aetiology of preeclampsia. However the role and the regulation of these substances is still not clear.
The aim of the present thesis was to study some of the genes expressed in the placenta that could be involved in the pathophysiology of preeclampsia and/or intrauterine growth restriction (IUGR). Consecutive biopsies of fresh placentas were collected from normal and preeclampsia-complicated placentas.
A placental tissue in vitro model was set up for experiments. For mRNA studies of endothelin-1, c-fos and c-jun, the progesterone receptor (PR) and the estrogen receptor (ER) we used a solution hybridisation method, which showed elevated expression of ET-1 and c-fos in IUGR placentas. The c-jun mRNA was significantly higher in the groups with preeclampsia and/or IUGR compared to controls. Furthermore, in situ hybridisation of the PR demonstrated it to be localised in endothelium, in fetal lymphocytes of placental capillaries and occasionally in matemal mononuclear cells. The PR protein content in the different groups showed that the level was decreased in severe preeclampsia but increased in mild preeclampsia compared to healthy controls. Measurement of progesterone content in placental tissue explants showed that addition of the antiprogestin RU-486 decreased the level of progesterone in the healthy placentas, whereas no such decrease was seen in the placentas from patients with preeclampsia after RU-486 treatment.
Furthermore the effect of the antiestrogen, ICI 182,780 was different in placentas from control and preeclamptic patients. eNOS immunosignal recorded by immunohistochemistry and confocal microscopy was significantly increased in the syncytiotrophoblasts of healthy placentas after ICI treatment but decreased in the preeclampsia placentas.
We suggest that an inadequate supply of progesterone, a deficiency in the mechanism of action of progesterone and/or an altered balance between the sex steroids produced by the placenta could influence not only the immune system but also the NO pathway and hereby contribute to several changes characteristic of preeclampsia.
Several biochemical changes in the placenta are evident. The nitric oxide (NO) system as well as the sex steroid hormones, estrogen and progesterone have been implicated in the aetiology of preeclampsia. However the role and the regulation of these substances is still not clear.
The aim of the present thesis was to study some of the genes expressed in the placenta that could be involved in the pathophysiology of preeclampsia and/or intrauterine growth restriction (IUGR). Consecutive biopsies of fresh placentas were collected from normal and preeclampsia-complicated placentas.
A placental tissue in vitro model was set up for experiments. For mRNA studies of endothelin-1, c-fos and c-jun, the progesterone receptor (PR) and the estrogen receptor (ER) we used a solution hybridisation method, which showed elevated expression of ET-1 and c-fos in IUGR placentas. The c-jun mRNA was significantly higher in the groups with preeclampsia and/or IUGR compared to controls. Furthermore, in situ hybridisation of the PR demonstrated it to be localised in endothelium, in fetal lymphocytes of placental capillaries and occasionally in matemal mononuclear cells. The PR protein content in the different groups showed that the level was decreased in severe preeclampsia but increased in mild preeclampsia compared to healthy controls. Measurement of progesterone content in placental tissue explants showed that addition of the antiprogestin RU-486 decreased the level of progesterone in the healthy placentas, whereas no such decrease was seen in the placentas from patients with preeclampsia after RU-486 treatment.
Furthermore the effect of the antiestrogen, ICI 182,780 was different in placentas from control and preeclamptic patients. eNOS immunosignal recorded by immunohistochemistry and confocal microscopy was significantly increased in the syncytiotrophoblasts of healthy placentas after ICI treatment but decreased in the preeclampsia placentas.
We suggest that an inadequate supply of progesterone, a deficiency in the mechanism of action of progesterone and/or an altered balance between the sex steroids produced by the placenta could influence not only the immune system but also the NO pathway and hereby contribute to several changes characteristic of preeclampsia.
List of papers:
I. Faxen M, Nasiell J, Lunell NO, Blanck A (1997). Differences in mRNA expression of endothelin-1, c-fos and c-jun in placentas from normal pregnancies and pregnancies complicated with preeclampsia and/or intrauterine growth retardation. Gynecol Obstet Invest. 44(2): 93-6.
Pubmed
II. Faxen M, Nasiell J, Lunell NO, Nisell H, Blanck A (1998). Altered placental mRNA expression of the progesterone but not the estrogen receptor in pregnancies complicated by preeclampsia. Hypertens Pregnancy. 17: 241-9.
III. Nasiell J, Papadogiannakis N, Carlstrom K, Enberg U, Olovsson M, Blanck A, Celsi G (2002). Progesterone and progesterone receptors in placentas from women with preeclampsia and from healthy pregnancies. [Submitted]
IV. Nasiell J, Nisell H, Blanck A, Lunell NO, Faxen M (1998). Placental expression of endothelial constitutive nitric oxide synthase mRNA in pregnancy complicated by preeclampsia. Acta Obstet Gynecol Scand. 77(5): 492-6.
Pubmed
V. Nasiell J, Blanck A, Celsi G, Brismar H (2002). Modulation of eNOS expression by ICI 182,780 in placentas from normal and preeclampsia-complicated pregnancies. [Submitted]
I. Faxen M, Nasiell J, Lunell NO, Blanck A (1997). Differences in mRNA expression of endothelin-1, c-fos and c-jun in placentas from normal pregnancies and pregnancies complicated with preeclampsia and/or intrauterine growth retardation. Gynecol Obstet Invest. 44(2): 93-6.
Pubmed
II. Faxen M, Nasiell J, Lunell NO, Nisell H, Blanck A (1998). Altered placental mRNA expression of the progesterone but not the estrogen receptor in pregnancies complicated by preeclampsia. Hypertens Pregnancy. 17: 241-9.
III. Nasiell J, Papadogiannakis N, Carlstrom K, Enberg U, Olovsson M, Blanck A, Celsi G (2002). Progesterone and progesterone receptors in placentas from women with preeclampsia and from healthy pregnancies. [Submitted]
IV. Nasiell J, Nisell H, Blanck A, Lunell NO, Faxen M (1998). Placental expression of endothelial constitutive nitric oxide synthase mRNA in pregnancy complicated by preeclampsia. Acta Obstet Gynecol Scand. 77(5): 492-6.
Pubmed
V. Nasiell J, Blanck A, Celsi G, Brismar H (2002). Modulation of eNOS expression by ICI 182,780 in placentas from normal and preeclampsia-complicated pregnancies. [Submitted]
Issue date: 2002-04-12
Rights:
Publication year: 2002
ISBN: 91-7349-154-3
Statistics
Total Visits
Views | |
---|---|
Expression ...(legacy) | 794 |
Expression ... | 129 |
Total Visits Per Month
January 2024 | February 2024 | March 2024 | April 2024 | May 2024 | June 2024 | July 2024 | |
---|---|---|---|---|---|---|---|
Expression ... | 2 | 0 | 0 | 0 | 0 | 3 | 1 |
File Visits
Views | |
---|---|
thesis.pdf(legacy) | 260 |
thesis.pdf | 68 |
thesis.pdf.txt(legacy) | 2 |
Top country views
Views | |
---|---|
United States | 361 |
China | 86 |
Sweden | 75 |
Germany | 51 |
Russia | 26 |
South Korea | 14 |
United Kingdom | 13 |
Finland | 8 |
Denmark | 6 |
Ireland | 6 |
Top cities views
Views | |
---|---|
Sunnyvale | 37 |
Romeo | 36 |
Beijing | 31 |
Kiez | 18 |
Seoul | 14 |
Shenzhen | 12 |
Stockholm | 12 |
Moscow | 10 |
Ashburn | 7 |
London | 7 |