Aspects of materno-fetal interactions in the placenta:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2006
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | VII, 117 Bl. Ill, graph. Darst. 30 cm |
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| 245 | 1 | 0 | |a Aspects of materno-fetal interactions in the placenta |c von Justine Sayuri Fitzgerald |
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Table of Contents
I. Introduction: (1)
A. History of Reproductive Immunology: (2)
B. Background in Reproduction and Selected
Pathologies: (4)
1. Immunity in the Human Female Reproductive
Tract: (4)
2. Fertilization, Decidualization, Implantation: (5)
a) Ovulation and Fertilisation: (5)
b) Implantation: (6)
c) Decidualisation: (8)
3. Placentation and Invasion: (9)
a) Placenta: (9)
b) Invasion: (13)
4. Selected Pathologies: (14)
a) Infertility: (15)
b) Recurrent Spontaneous Abortion: (15)
c) Human Choriocarcinoma: (16)
C. Selected, Recent Hypotheses to Explain Materno-
fetal Tolerance: (17)
1. HLA-G: (18)
2. The Thi-Th2 Paradigm: (20)
3. Tryptophan Catabolism: (21)
ii
4. Leukemia Inhibitory Factor (LIF): (22)
5. Hormones and Other Soluble Factors: (23)
D. Cytokines: (24)
1. A Selection of THi Type Cytokines: (25)
a) L£. (25)
b) Interferon (IFN) - r. (26)
2. A Selection of TH2 Type Cytokines: (27)
a) JL4: (27)
b) JMO: (27)
£ Signal Transduction: (28)
1. The Jak-Stat-Signal Transducing Pathway: (28)
2. Stat 3 and its Relevance to Reproduction: (29)
II. Ajms: (30)
III. Material and Methods: (33)
A. General Methodology: (33)
1. Ovine Uterine Serpine (OvUS) Purification: (33)
2. Lymphocyte Isolation: (34)
3. Lymphocyte Culture: (34)
4. Lymphocyte Proliferation Assay: (34)
5. Human Choriocarcinoma Cell Line and Culture: (35)
6. Long Term Cell Proliferation Assay: (35)
7. Trophoblast Cell Isolation: (36)
iii
a) Kliman Protocol: (36)
b) Lala Protocol: (37)
8. Trophoblast Cell Culture and Placenta Explant
Supernatant: (38)
9. Flow Cytometry: (38)
10. Lysing of Cells, Polyacrylamid Gel
Electrophoresis and Western Blot: (39)
11. Electrophoretic Mobility Shift Assay (EMSA): (40)
12. Protease Expression Analysis by cDNA Arrays: (42)
13. Quantification of Specific mRNAs by Real Time PCR: (44)
14. In Vitro Cell Invasion Assay: (44)
15. Ethical considerations: (45)
B. Specific Methodology: (46)
1. OvUS and lymphocytes: TH2-Shift (46)
2. Tryptophan Catabolism and Lymphocytes: Th2-
Shift and JaK-Stat (47)
a) TH2 Shift: (47)
b) JaK-Stat: (49)
3. Trophoblast Invasion and JaK-Stat (50)
4. Human Choriocarcinoma Cell (hCC) Invasion and
Cytokines: JaK-Stat (51)
5. Trophoblast Invasion and Cytokines: JaK-Stat (54)
iv
IV. Results: (55)
A. Hypothesis 1: OvUS induces a TH?-shift in human
peripheral blood lymphocytes (PBL):
1. OvUS decreases the expression of CD69 and
CD71 in a dose dependent manner in human
lymphocytes. (55)
2. OvUS increases the expression of IL-2 receptor
chains in a dose-dependent manner on human
lymphocytes. (55)
3. OvUS induces a Ttu-prone interleukin profile in
CD3+ human lymphocytes. (56)
B. Hypothesis 2: Tryptophan depletion through IPO
activity of trophoblast supernatants
leads to Tm-shift in human PBL
regulated through Stat3 expression
and phosphorylation: (57)
a) ad Hypotheses 2a: Trophoblast supernatants
display IDO activity. (57)
and
b) ad Hypotheses 2b: IDO activity of trophoblast
supernatants leads to a Th2 shift in human
PBL (57)
1. Trophoblast supernatants suppressed PHA
mediated proliferation of lymphocytes. (57)
2. Trophoblast supernatants suppressed PHA
mediated up-regulation of Tm type surface
molecules in CD3+ human peripheral blood
lymphocytes. (57)
V
3. First trimester placenta explant supernatants
display IDO activity. (58)
4. Term trophoblast supernatants display no
significant IDO activity. (58)
5. IDO activity in first trimester trophoblast
supernatants alters only CD 154 expression. (59)
c) TH2 shift in human PBL through IDO activity
is Stat3-mediated. (59)
1. IDO activity reduces steady-state levels of Stat3 in
human peripheral blood lymphocytes. (59)
2. IDO activity increases tyrosine phosphorylation of
Stat3 in human peripheral blood lymphocytes.
(60)
C. Hypothesis 3: Trophoblast and hCC invasion positively
correlates with Stat3 avitvity. (61)
1. DNA binding activity of Stat3 in trophoblast cells
is lost in progressing pregnancy. (61)
2. Stat3 is constitutively active in choriocarcinoma
cells. (62)
D. Hypothesis 4: Jeq3- hCC invasion and proliferation
can be stimulated by cytokines
through regulation of Stat3 activation.
(63J
vi
1. LIF induces tyrosine phosphorylation of Stat3 in
choriocarcinoma cells. (63)
2. LIF enhances proliferation and invasiveness of
choriocarcinoma cells. (63)
3. LIF elicits specific DNA binding activity of Stat3 in
choriocarcinoma cells. (64)
4. LIF affects the expression of a protease and a
protease inhibitor involved in cell invasiveness.
(65)
E. Hypothesis 5: Trophoblast invasion can be stimulated
by cvtokines through regulation of Stat3
activation. (65)
1. LIF induces tyrosine phosphorylation of Stat3 in
term trophoblast cells. (66)
V. Discussion: (67)
A. ad 1. Hypothesis: (67)
OvUS - an evolutionary protein that led to revolutionary reproduction? (67)
What did OvUS teach us? (68)
Could there be a new role for OvUS in Treg and TW cells? (68)
Where might OvUS lead us to next? (69)
B. ad 2. Hypothesis: (70)
It takes IDO to tango (70)
Much IDO about trophoblast (70)
A tale of two methods (72)
CD154(73)
Food for the future (73)
IDO and signaling - the potential of Stat3 (74)
The terms of supernatant (75)
vii
Great unexpectations (75)
Beyond the looking glass (77)
Sense and sensibility (78)
C. ad 3., 4. and 5. Hypothesis: (79)
Know thy enemy (79)
All for one (80)
One for all (81)
LIF and let LIF (83)
VI. Bibliography (85)
VII. List of Abbreviations / Glossary (102)
VIII. Table Figures (115)
|
| adam_txt |
i
ooooooooooooo
Table of Contents
I. Introduction: (1)
A. History of Reproductive Immunology: (2)
B. Background in Reproduction and Selected
Pathologies: (4)
1. Immunity in the Human Female Reproductive
Tract: (4)
2. Fertilization, Decidualization, Implantation: (5)
a) Ovulation and Fertilisation: (5)
b) Implantation: (6)
c) Decidualisation: (8)
3. Placentation and Invasion: (9)
a) Placenta: (9)
b) Invasion: (13)
4. Selected Pathologies: (14)
a) Infertility: (15)
b) Recurrent Spontaneous Abortion: (15)
c) Human Choriocarcinoma: (16)
C. Selected, Recent Hypotheses to Explain Materno-
fetal Tolerance: (17)
1. HLA-G: (18)
2. The Thi-Th2 Paradigm: (20)
3. Tryptophan Catabolism: (21)
ii
4. Leukemia Inhibitory Factor (LIF): (22)
5. Hormones and Other Soluble Factors: (23)
D. Cytokines: (24)
1. A Selection of THi Type Cytokines: (25)
a) \L£. (25)
b) Interferon (IFN) - r. (26)
2. A Selection of TH2 Type Cytokines: (27)
a) JL4: (27)
b) JMO: (27)
£ Signal Transduction: (28)
1. The Jak-Stat-Signal Transducing Pathway: (28)
2. Stat 3 and its Relevance to Reproduction: (29)
II. Ajms: (30)
III. Material and Methods: (33)
A. General Methodology: (33)
1. Ovine Uterine Serpine (OvUS) Purification: (33)
2. Lymphocyte Isolation: (34)
3. Lymphocyte Culture: (34)
4. Lymphocyte Proliferation Assay: (34)
5. Human Choriocarcinoma Cell Line and Culture: (35)
6. Long Term Cell Proliferation Assay: (35)
7. Trophoblast Cell Isolation: (36)
iii
a) Kliman Protocol: (36)
b) Lala Protocol: (37)
8. Trophoblast Cell Culture and Placenta Explant
Supernatant: (38)
9. Flow Cytometry: (38)
10. Lysing of Cells, Polyacrylamid Gel
Electrophoresis and Western Blot: (39)
11. Electrophoretic Mobility Shift Assay (EMSA): (40)
12. Protease Expression Analysis by cDNA Arrays: (42)
13. Quantification of Specific mRNAs by Real Time PCR: (44)
14. In Vitro Cell Invasion Assay: (44)
15. Ethical considerations: (45)
B. Specific Methodology: (46)
1. OvUS and lymphocytes: TH2-Shift (46)
2. Tryptophan Catabolism and Lymphocytes: Th2-
Shift and JaK-Stat (47)
a) TH2 Shift: (47)
b) JaK-Stat: (49)
3. Trophoblast Invasion and JaK-Stat (50)
4. Human Choriocarcinoma Cell (hCC) Invasion and
Cytokines: JaK-Stat (51)
5. Trophoblast Invasion and Cytokines: JaK-Stat (54)
iv
IV. Results: (55)
A. Hypothesis 1: OvUS induces a TH?-shift in human
peripheral blood lymphocytes (PBL):
1. OvUS decreases the expression of CD69 and
CD71 in a dose dependent manner in human
lymphocytes. (55)
2. OvUS increases the expression of IL-2 receptor
chains in a dose-dependent manner on human
lymphocytes. (55)
3. OvUS induces a Ttu-prone interleukin profile in
CD3+ human lymphocytes. (56)
B. Hypothesis 2: Tryptophan depletion through IPO
activity of trophoblast supernatants
leads to Tm-shift in human PBL
regulated through Stat3 expression
and phosphorylation: (57)
a) ad Hypotheses 2a: Trophoblast supernatants
display IDO activity. (57)
and
b) ad Hypotheses 2b: IDO activity of trophoblast
supernatants leads to a Th2 shift in human
PBL (57)
1. Trophoblast supernatants suppressed PHA
mediated proliferation of lymphocytes. (57)
2. Trophoblast supernatants suppressed PHA
mediated up-regulation of Tm type surface
molecules in CD3+ human peripheral blood
lymphocytes. (57)
V
3. First trimester placenta explant supernatants
display IDO activity. (58)
4. Term trophoblast supernatants display no
significant IDO activity. (58)
5. IDO activity in first trimester trophoblast
supernatants alters only CD 154 expression. (59)
c) TH2 shift in human PBL through IDO activity
is Stat3-mediated. (59)
1. IDO activity reduces steady-state levels of Stat3 in
human peripheral blood lymphocytes. (59)
2. IDO activity increases tyrosine phosphorylation of
Stat3 in human peripheral blood lymphocytes.
(60)
C. Hypothesis 3: Trophoblast and hCC invasion positively
correlates with Stat3 avitvity. (61)
1. DNA binding activity of Stat3 in trophoblast cells
is lost in progressing pregnancy. (61)
2. Stat3 is constitutively active in choriocarcinoma
cells. (62)
D. Hypothesis 4: Jeq3- hCC invasion and proliferation
can be stimulated by cytokines
through regulation of Stat3 activation.
(63J
vi
1. LIF induces tyrosine phosphorylation of Stat3 in
choriocarcinoma cells. (63)
2. LIF enhances proliferation and invasiveness of
choriocarcinoma cells. (63)
3. LIF elicits specific DNA binding activity of Stat3 in
choriocarcinoma cells. (64)
4. LIF affects the expression of a protease and a
protease inhibitor involved in cell invasiveness.
(65)
E. Hypothesis 5: Trophoblast invasion can be stimulated
by cvtokines through regulation of Stat3
activation. (65)
1. LIF induces tyrosine phosphorylation of Stat3 in
term trophoblast cells. (66)
V. Discussion: (67)
A. ad 1. Hypothesis: (67)
OvUS - an evolutionary protein that led to revolutionary reproduction? (67)
What did OvUS teach us? (68)
Could there be a new role for OvUS in Treg and TW cells? (68)
Where might OvUS lead us to next? (69)
B. ad 2. Hypothesis: (70)
It takes IDO to tango (70)
Much IDO about trophoblast (70)
A tale of two methods (72)
CD154(73)
Food for the future (73)
IDO and signaling - the potential of Stat3 (74)
The terms of supernatant (75)
vii
Great unexpectations (75)
Beyond the looking glass (77)
Sense and sensibility (78)
C. ad 3., 4. and 5. Hypothesis: (79)
Know thy enemy (79)
All for one (80)
One for all (81)
LIF and let LIF (83)
VI. Bibliography (85)
VII. List of Abbreviations / Glossary (102)
VIII. Table Figures (115) |
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| dewey-ones | 612 - Human physiology |
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| spelling | Fitzgerald, Justine Sayuri 1973- Verfasser (DE-588)133574598 aut Aspects of materno-fetal interactions in the placenta von Justine Sayuri Fitzgerald 2006 VII, 117 Bl. Ill, graph. Darst. 30 cm txt rdacontent n rdamedia nc rdacarrier Jena, Univ., Diss., 2007 (DE-588)4113937-9 Hochschulschrift gnd-content HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016294365&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Fitzgerald, Justine Sayuri 1973- Aspects of materno-fetal interactions in the placenta |
| subject_GND | (DE-588)4113937-9 |
| title | Aspects of materno-fetal interactions in the placenta |
| title_auth | Aspects of materno-fetal interactions in the placenta |
| title_exact_search | Aspects of materno-fetal interactions in the placenta |
| title_exact_search_txtP | Aspects of materno-fetal interactions in the placenta |
| title_full | Aspects of materno-fetal interactions in the placenta von Justine Sayuri Fitzgerald |
| title_fullStr | Aspects of materno-fetal interactions in the placenta von Justine Sayuri Fitzgerald |
| title_full_unstemmed | Aspects of materno-fetal interactions in the placenta von Justine Sayuri Fitzgerald |
| title_short | Aspects of materno-fetal interactions in the placenta |
| title_sort | aspects of materno fetal interactions in the placenta |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=016294365&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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