| Abstract |
The corticotropin-releasing factor (CRF) and its family molecules the
urocortins (UCNI, UCNII, UCNIII) are the major regulators and coordinators of the
behavioral, endocrine and immune responses of the human organism to stress. The
effects of these peptides are mediated by two types of receptors the CRFR1 and
CRFR2. The peptides and their receptors are localized in the central nervous system,
as well as in a variety of peripheral tissues, including almost all of the tissues of the
reproductive tract.
The biological role of the “reproductive” CRF system is under investigation.
The peptides have been found to participate as paracrine and/or autocrine modulators
in important functions of the reproductive system, such as ovulation, lutealizasion,
blastocyst implantation, decidualization, function of embryo-placental circulation and
parturition. In addition, defects of the local CRF system, is thought to be involved in
the pathophysiology of the above functions.
In the present study, the role of CRF and CEACAM1 peptides in the
physiology of trophoblast invasion as well as the role of CRF, UCN and pro-apoptotic
Fas/FasL peptides in implantation failure were investigated. The study also examined
the effect of decidual lymphocytes on extravillous trophoblasts (EVT) as a potential
element of the cellular and molecular mechanisms involved in the pathophysiology of
miscarriages.
The data presented here, report that CRF reduces the invasive potential of
isolated EVT cells. This effect was mediated by CRFR1 and was owed to downregulation
of the expression of the adhesion molecule CEACAM1 in the surface of
the cells. Blocking of CEACAM1 in the same cells resulted to significant reduction of
their invasiveness. In addition, an EVT-based cell line which does not express
CEACAM1 was employed. Transfection of these cells with the CEACAM1 gene, led
to significant increase of their invasiveness.
Next, the following findings were reported. UCN is expressed at the
implantation site of the human embryo and more specifically in the EVT of 1st
trimester normal placentas. Spontaneous abortion in human is associated with
increased expression of CRF and UCN at the implantation site, increased expression
of FasL in the decidual leukocytes and increased expression of Fas in EVT cells. The
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aforementioned molecules were examined both at the level of transcript and
translational products. In addition, spontaneous abortions are associated with
increased apoptosis of interstitial EVT cells. Finally, the CRF and UCN peptides
augment the ability of decidual lymphocytes to induce Fas-mediated apoptosis in the
EVT-based cell line.
In conclusion, the present study reports novel findings on the role of CRF and
UCN in human blastocyst implantation and subsequent placentation, as well as in the
impairment of the above procedures.
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Μελέτη της έκφρασης, της ρύθμισης και του βιολογικού ρόλου της εκλυτικής ορμόνης της κορτικοτροπίνης (CRH) στη θέση εμφύτευσης του ανθρώπινου εμβρύου
