Blastocyst implantation failure relates to impaired translational machinery gene expression

Abstract

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.Reproduction (2014) 148 87-98

An integrated genome-wide multi-omics analysis of gene expression dynamics in the preimplantation mouse embryo

“…Translation in the preimplantation embryo is limited by the availability of free ribosomes, which are the most active players of a cell’s translational machinery, but poorly represented in pre-morula-stage mouse embryos. This explains why an impaired translational machinery does not affect blastocyst formation, but causes blastocyst implantation failure in mice 62 .…”

Lost in translation: egg transcriptome reveals molecular signature to predict developmental success and novel maternal-effect genes

“…This seems somewhat contradictory due to the fact that most bad quality eggs eventually die and an accumulation in ribosomes is usually a sign of increased cell proliferation and growth[32]. It is well-known that ribosome biogenesis deficiency often leads to an impairment in cell growth and to cell death while elevated ribosomal function results in increased cell cycle progression and proliferation[33]. Thus, it is possible that the increased ribosomal content and presumably elevated translation that were found in bad quality eggs may reflect dysregulated cell cycle progression and cell growth, which in fact may lead to premature cell death as shown by pathological models in which loss of cell cycle and cell death regulators lead to disease[34,35].…”

An integrated genome-wide multi-omics analysis of gene expression dynamics in the preimplantation mouse embryo

“…Translation in the preimplantation embryo is limited by the availability of free ribosomes, which are the most active players of a cell's translational machinery, but poorly represented in pre-morula-stage mouse embryos. This explains why an impaired translational machinery does not affect blastocyst formation, but causes blastocyst implantation failure in mice (Plaks et al 2014).…”