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Activation of uterine innate immune system affects embryo im
Transcript of Activation of uterine innate immune system affects embryo im
Interaction between the blastocyst and endometrium epithelium.
Window of implantation. Late secretory phase. Between days LH+5 +7.
Guarantee the success of pregnancy.
Causes leading to infertility
Javier Arturo Sánchez-López
Limitations and deficiencies
Impossible to evaluate clinically.
Highly inefficient 1 in 2 embryos implant.
World fertility rates decline.
Assisted conception techniques require more research to increase effectiveness.
What we know
- Molecular characteristics acquired by the endometrial cells for interaction with the embryonic trophoblasts
- Adhesion molecules:
Sialyl Lexis X
- Extracellular Matrix
- Microvillous surface
Can endometrial receptivity be affected?
Can the endometrium react to this stimuli?
Adapted from Nat Immunol, 2010 vol. 11 (5) pp. 373-84
The Toll-like Receptor Family sense pathogens
Can the uterus express these TLRs?
Expression of the TLRs in the uterus
Influenced by hormonal status
Endometrial TLR activation decreases trophoblast adhesion in vitro
Highest expression at the late secretory phase
Can endometrial TLR activation affect embryo implantation?
Endometrial cell line RL95-2
Choriocarcinoma - JAr cells
Choriocarcinoma spheroids - JAr Cells
In vitro implantation model
Endometrial TLR 5 activation decreases trophoblast spheroid adhesion
Aflatoonian, et al; Hum Reprod; 2007
Aboussahoud W., et al, Hum Reprod, 2010
TLR 2, 2/6 - Gram+
TLR 3 - Virus
TLR 9 - Intracellular bacteria
How does endometrial TLR activation affects the intercellular adhesion?
Visualisation of endometrial cell microscopical structures
Allows to obtain 3D topography images of the cells
Mucosal immune responses
Mucin - Highly glycosilated membrane proteins:
Produced in gut and lungs during infections.
Present in the endometrium previous to implantation.
Absent in the implantation site.
TLR Signalling pathways
In vivo embryo implantation murine model
Verify the biological effect in vivo.
TLR activation induced
TLR 2/6 and TLR 3 Stimulation
Loss of microvilli and membrane blebbing
Time lapse measurements
Detrimental effect in tissue architecture
Effects in embryo implantation
FSL-1 treatment increased:
Key cytokines for
Simulated infection. Flagellin - TLR 5
A) Assessment the role of TLR 5 activation during the embryo implantation process. (Already performed)
Raúl Fernández González