Blastocyst implantation failure relates to impaired translational machinery gene expression.
Oocyte quality is a well-established determinant of embryonic fate. However, the molecular participants and biological markers that affect and may predict adequate embryonic development are largely elusive. Our aim was to identify the components of the oocyte molecular machinery that part take in the production of a healthy embryo. For this purpose, we used an animal model, generated by us previously, the oocytes of which do not express Cx43 (Cx43(del/del)). In these mice, oogenesis appears normal, fertilisation does occur, early embryonic development is successful but implantation fails. We used magnetic resonance imaging analysis combined with histological examination to characterise the embryonic developmental incompetence. Reciprocal embryo transfer confirmed that the blastocyst evolved from the Cx43(del/del) oocyte is responsible for the implantation disorder. In order to unveil the genes, the impaired expression of which brings about the development of defective embryos, we carried out a genomic screening of both the oocytes and the resulting blastocysts. This microarray analysis revealed a low expression of Egr1, Rpl21 and Eif4a1 in Cx43(del/del) oocytes and downregulation of Rpl15 and Eif4g2 in the resulting blastocysts. We propose that global deficiencies in genes related to the expression of ribosomal proteins and translation initiation factors in apparently normal oocytes bring about accumulation of defects, which significantly compromise their developmental capacity. The blastocysts resulting from such oocytes, which grow within a confined space until implantation, may be unable to generate enough biological mass to allow their expansion. This information could be implicated to diagnosis and treatment of infertility, particularly to IVF.
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel.
Vicki
V
Plaks
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel.
Eran
E
Gershon
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel.
Amit
A
Zeisel
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel.
Jasmine
J
Jacob-Hirsch
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel.
Michal
M
Neeman
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel.
Elke
E
Winterhager
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel.
Gideon
G
Rechavi
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel.
Eytan
E
Domany
Departments of Biological RegulationPhysics of Complex SystemsThe Weizmann Institute of Science, Rehovot 76100, IsraelInstitute of AnatomyUniversity Hospital Duisburg-Essen, Essen, GermanyThe Sheba Cancer Research CenterSheba Medical Center, Tel Hashomer, Israel Nava.dekel@weizmann.ac.il.
Nava
N
Dekel
D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D018031:Connexin 43 / Q000172:deficiency / Q000235:genetics; D010065:Embryo Implantation, Delayed / Q000235:genetics*; D004624:Embryo Transfer; D039642:Eukaryotic Initiation Factors / Q000172:deficiency / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008279:Magnetic Resonance Imaging; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D014176:Protein Biosynthesis / Q000235:genetics*; D012269:Ribosomal Proteins / Q000172:deficiency / Q000235:genetics
D018031:Connexin 43; D039642:Eukaryotic Initiation Factors; C543076:GJA1 protein, mouse; D012269:Ribosomal Proteins