Global, Survival, and Apoptotic Transcriptome during Mouse and Human Early Embryonic Development.

D Haouzi,K Chebli,I Boumela,S Hamamah

doi:10.1155/2018/5895628

Abstract

Survival and cell death signals are crucial for mammalian embryo preimplantation development. However, the knowledge on the molecular mechanisms underlying their regulation is still limited. Mouse studies are widely used to understand preimplantation embryo development, but extrapolation of these results to humans is questionable. Therefore, we wanted to analyse the global expression profiles during early mouse and human development with a special focus on genes involved in the regulation of the apoptotic and survival pathways. We used DNA microarray technology to analyse the global gene expression profiles of preimplantation human and mouse embryos (metaphase II oocytes, embryos at the embryonic genome activation stage, and blastocysts). Components of the major apoptotic and survival signalling pathways were expressed during early human and mouse embryonic development; however, most expression profiles were species-specific. Particularly, the expression of genes encoding components and regulators of the apoptotic machinery were extremely stable in mouse embryos at all analysed stages, while it was more stage-specific in human embryos. CASP3, CASP9, and AIF were the only apoptosis-related genes expressed in both species and at all studied stages. Moreover, numerous transcripts related to the apoptotic and survival pathway were reported for the first time such as CASP6 and IL1RAPL1 that were specific to MII oocytes; CASP2, ENDOG, and GFER to blastocysts in human. These findings open new perspectives for the characterization and understanding of the survival and apoptotic signalling pathways that control early human and mouse embryonic development.

Highlights

The ability of early mammalian embryos to cope with stress during the first stages of development could be controlled by the activation of survival pathways through autocrine and paracrine regulatory signals [1], and by the establishment of a cell death program to ensure the elimination of damaged cells [2, 3]
A first selection of genes using a coefficient of variation (CV)≥40% and a present detection call in at least 50% of the three comparison groups of human samples (i.e., metaphase II (MII) oocytes versus day 3 embryos, MII oocytes versus day 5/6 blastocysts, and day 3 embryos versus day 5/6 blastocysts) identified 7618, 9660, and 8239 genes, respectively
SAM analyses of these selected gene lists identified 5170, 7725, and 5372 genes that were differentially expressed in MII oocytes compared with day 3 embryos (EGA), MII oocytes compared with day 5/6 blastocysts, and day 3 embryos (EGA) compared with day 5/6 blastocysts, with a similar proportion of upregulated and downregulated genes in each comparison (Figure 1(a), Supplementary Table S2, S3, and S4)

Summary

Introduction

The ability of early mammalian embryos to cope with stress during the first stages of development could be controlled by the activation of survival pathways through autocrine and paracrine regulatory signals [1], and by the establishment of a cell death program to ensure the elimination of damaged cells [2, 3]. Apoptosis has been described in human and animal oocytes and early embryos in vitro and in vivo [4, 5]. Sensitivity to apoptosis appears to be developmentally regulated [6], suggesting that a fine balance between apoptotic and survival signals is established in preimplantation embryos. Our group showed that some genes implicated in the apoptotic machinery are expressed in human and animal oocytes and early embryos [3, 9]. To better understand these processes we need to BioMed Research International

Methods

Results

Conclusion