| Abstract |
Despite the improvements in technology and know-how in human assisted reproduction, pregnancy rates
remain low due to an imbalanced interaction between the embryo and the uterus upon ovarian stimulation.
The normal reproductive process is controlled by a set of interactions that take place either among cells or
between cells and the extracellular matrix (ECM). Such interactions involve cells, ligands, cell adhesion
molecules, adhesion molecules that mediate cell-to-cell and cell-to-ECM interactions, as well as their
receptors. The most important groups of these receptors are integrins and cadherins, which are
characterized as adhesion molecules located on the cell surface. Integrins are a family of cell surface
glycoprotein receptors that are involved in both intercellular and extracellular molecule binding, thereby
allowing the organization of cells and tissues. From invertebrates to vertebrates, integrins and cadherins
have been shown to play an important role in fertilization, embryo development and placentation.
Specifically in mammals, ECM interactions with the epithelium hosting each embryonic stage play a
critical role in the fate of the developing embryo, its ability to migrate to the uterus, to implant and grow
until birth. This study presents new data on the involvement of adhesion molecules in the reproductive
process. In order to investigate the role of cellular interactions with extracellular space molecules in the
reproductive process, we studied the effect of the ovarian stimulation protocol and embryo biopsy on the
expression of fetal integrins and cadherins, as well as their possible regulation of expression in the
presence of L-carnitine (L-Cn). We focused on the expression of the integrins avb3, α5b1, av, α6b1 and
E-cadherin in zygotes and different stages of embryos grown in vitro or isolated directly from the animal
in vivo. Only the in vivo developing embryos showed a specific and polarized distribution of these
molecules, indicating their possible successful interaction with the endometrium. The results presented in
this study showed that an embryo that is considered to be healthy, according to the morphological criteria
by microscopic observation, may be unsuitable for implantation due to the abnormal expression of
adhesion molecules. The observation that fetal biopsy reduces the expression of adhesion molecules, most
likely due to the invasive nature of the technique, could explain the failure of morphologically and
genetically healthy embryos to implant. The addition of L-Cn to the embryonic culture medium, as a
powerful energy generating factor, has been shown to enhance the expression of adhesion molecules in
pre-implantation embryos, simulating thus the in vivo phenotype of adhesion molecules in the developing
embryos, which is important for the acquisition of early embryo polarisation. Early polarity determines
the subsequent development of the embryo and its successful implantation. Within the organism, such
polarity is dictated by the tubal epithelial cells through interactions with the adhesion molecules, which is
not observed in the in vitro developing embryos. Further development of the technology could provide
biomimetic surfaces resembling the tubal environment, thereby providing a natural developmental
environment for the embryos, and thus an improved embryo implantation outcome.
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