The unique transcriptome through day 3 of human preimplantation development

Abstract

Successful human development is dependent upon a cascade of events following fertilization. Unfortunately, knowledge of these critical events in humans is remarkably incomplete. Although hundreds of thousands of human embryos are cultured yearly at infertility centers worldwide, the vast majority fail to develop in culture or following transfer to the uterus. In this study, we sought to characterize global patterns of gene expression in individual, normal embryos during the first three days of embryonic life using microarrays; we then compared gene expression between normally growing and growth-arrested embryos using quantitative PCR. Our results documented several novel findings. First, we found that a complex pattern of gene expression exists; most genes that are transcriptionally modulated during the first three days following fertilization are not upregulated, as was previously thought, but are downregulated. Second, we observed that the majority of genes exhibiting differential expression during preimplantation development are of unknown identity and/or function. Third, we show that embryonic transcriptional programs are clearly established by day 3 following fertilization, even in embryos that arrested prematurely with 2-, 3- or 4-cells. This indicates that failure to activate transcription is not associated with the majority of human preimplantation embryo loss. Finally, taken together, these results provide the first global analysis of the human preimplantation embryo transcriptome, and demonstrate that RNA can be amplified from single oocytes and embryos for analysis by cDNA microarray technology, thus lending credence to additional studies of genetic regulation in these cell types, as well as in other small biological samples.

Supplementation of fetal bovine serum alters histone modification H3R26me2 during preimplantation development of in vitro produced bovine embryos

“…the 8-cell stage and another increase to the blastocyst stage (Zhang et al 2012). These authors suggest the changes observed for both H3K4me3 and H3K27me3 from the 4-cell to 8-cell stage may be associated with embryonic genome activation, (Zhang et al 2012) which occurs during this time in human embryos (Dobson et al 2004).…”

A Comparative Analysis Between Day 2 and Day 3 Embryo Transfer in IVF/ICSI: A Retrospective Cross-Sectional Study

“…Although in these studies, in patients with good prognosis, fewer embryos were transferred, in our survey, between the two groups, the number of embryos transferred remained unchanged. Many studies also compared day 2 with day 3 ETs, but there seems to be no consensus (4,5,21,22). For example, Laverge et al (6) observed similar clinical pregnancy and implantation rates between days 2 and 3, while overall embryo quality scores were lower on day 3.…”

“…However, in another study it was suggested that the embryo selection occurs during the cleavage period. Therefore, a delay in ET to day 3 may lead to selection of better quality embryos for transfer (22). In a retrospective study, Dawson et al (7) showed that the pregnancy rate was higher with day 3 ET, but this was not statistically significant (35% vs. 31%, NS); however, implantation rates showed a significant difference (23% vs. 19%, P < 0.05) and the miscarriage rate was lower on day 3(6% vs. 2%, P < 0.05).…”

Selecting a Single Embryo for Transfer after In-vitro Fertilization: A Translational Medicine Perspective

“…In human, the embryonic gene becomes active at 4-8 cell stage which is maintained throughout adult life. Dobson et al, [70] reported several studies that documented key events that follow fertilization in humans, such as a decrease in abundance of individual mRNAs, activation of bulk mRNA transcription following a quiescent period and nascent expression of a few individual known genes that were previously characterized in other organisms. They also validated reports that demonstrate robust patterns of stage specific gene expression, representing maternal genes that are deactivated (down-regulated) and zygotic genes that are activated (upregulated) using their microarray studies.…”