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Prostaglandin E2 and prostaglandin F2 alpha as endometrial receptivity biomarkers in successful embryo implantation

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Prostaglandin E2 and prostaglandin F2 alpha as endometrial receptivity biomarkers in successful embryo implantation

dc.contributor.advisor	Simón Vallés, Carlos
dc.contributor.advisor	Vilella Mitjana, Felipe
dc.contributor.author	Ramirez Lima, Leslie Berenice
dc.contributor.other	Facultat de Ciències Biològiques	es_ES
dc.date.accessioned	2014-02-17T08:16:18Z
dc.date.available	2014-02-18T07:10:03Z
dc.date.issued	2014
dc.date.submitted	21-02-2014	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/32957
dc.description.abstract	Failure in the adhesion of the human blastocyst to the endometrium has been described as an important cause of infertility. Establishing the period of the so-called window of implantation and understanding the molecular mechanisms associated with embryo implantation has clinical and scientific implications. While over the last decades histological evaluation has been used to determine the phase of the menstrual cycle of the endometrium, the poor information obtained has made the case of using new technologies to identify specific markers, understand and characterize the receptive stage. This doctoral thesis investigates the existence, function and clinical impact of two specific lipids, the prostaglandins E(2) and F(2α), which are abundant in human endometrial fluid (EF) during the window of implantation in natural, IVF, and ovum recipient cycles, which is abrogated with the insertion of an IUD. Developments in endometrial receptivity diagnosis using lipidomics demonstrate the correlation between those prostaglandins (PGs) and the receptive stage of the endometrium. The mechanisms that influence the production of these individual PGs in the endometrium were studied with a clinical approach that sheds light on the sequence of events that leads to the development of endometrial receptivity. Our results indicate that PG synthases required for the production of PGE2 and PGF2α are located in the endometrial epithelium and EF for the regulation of PGs concentrations during the window of implantation. Most of the accumulated evidence, using an in vitro model of embryonic adhesion, indicates that inhibition of PGE2 and PGF2α or the PG receptors EP2 and FP prevents embryo adhesion, which can be reversed by adding back these molecules or by using EP2 and FP agonists. Finally, our pilot study demonstrates that PGE2 and PGF2α concentrations in EF aspirated 24 hours prior to embryo transfer showed to be predictive of a successful pregnancy outcome. In summary, our findings indicate that embryo implantation is associated with an active crosstalk of PGE2 and PGF2α via EP2 and FP receptors, respectively, that might serve to nurse the blastocyst at the time of embryo implantation. Likewise the levels of these PGs in EF could potentially serve as non-invasive biomarkers to define the receptive phase of the endometrium and, therefore, have a significant impact in clinical translation.	es_ES
dc.format.extent	194 p.	es_ES
dc.language.iso	en	es_ES
dc.subject	infertility	es_ES
dc.subject	endometrial receptivity	es_ES
dc.subject	prostaglandins	es_ES
dc.subject	biomarkers	es_ES
dc.title	Prostaglandin E2 and prostaglandin F2 alpha as endometrial receptivity biomarkers in successful embryo implantation	es_ES
dc.type	doctoral thesis	es_ES
dc.subject.unesco	UNESCO::CIENCIAS DE LA VIDA	es_ES
dc.embargo.terms	0 days	es_ES