Review ArticleTranscriptional profiling to address molecular determinants of endometrial receptivity – Lessons from studies in livestock species
Highlights
► Livestock species provide suitable models for studying issues of endometrial receptivity. ► Transcriptomic data need careful evaluation in targeted approaches. ► Endometrial transcriptomics allow upstream analysis of signal fingerprints. ► Transcriptional profiling may unravel embryonic signaling in livestock species. ► Endometrial biomarkers may be used for embryo quality assessment.
Section snippets
Endometrial function in livestock species
Remodeling and differentiation processes in the female reproductive system during the sexual cycle and pregnancy provide a perfectly synchronized environment for final maturation of gametes, fertilization, embryonic development, and for the establishment of pregnancy. Hormones have a major impact on the physiological status of the endometrium [1]. At the site of ovulation, the functional corpus luteum develops and produces progesterone (P4) to sustain the secretory property of the endometrium.
Animal models for the study of early embryo-maternal communication
Suitable in vivo and in vitro approaches are necessary to disentangle participating factors important for successful recognition and establishment of pregnancy.
In general, working with the species of interest is most favorable due to species-specific differences mentioned above. Although differences may be only small, a matter of quantity or timing, they could lead to wrong conclusions due to different use of inter- and intracellular pathways (i.e., for recognition of pregnancy, different
Tissue sampling and material quality demands
In general, good biological models require a proper experimental design, adapted to the biological question to be resolved. In addition to technical variance, the biological alteration is the major source for variation in the results of gene expression studies and has to be considered for making an experimental design (i.e., biological replicates are required and the number of replicates depends on the variability) [47]. Biological variability can be caused for example by differences in tissue
Transcriptomics for analysis of differential gene expression
Mammalian genomes contain approximately 20,000–22,000 protein-coding genes and a growing number of genes for structural and regulatory RNAs. The number of individual transcripts encoded by mammalian genomes is significantly higher due to transcript isoforms arising from the same gene [54], [55], [56], [57]. Furthermore, all the RNAs contained in a given tissue occur in very different abundances [54], [58] making the parallel analysis of all RNAs contained in a sample a technical challenge.
Downstream analysis of single candidate genes – endometrial functions
In general, differential gene expression allows the presumption of gene products involved in a particular function and the generation of hypotheses. But unfortunately, descriptive data are limited, because it is challenging to disentangle causes from concomitant incidences, which are independent. In the context of biological communication, it is not at all obvious to distinguish signals as initial setters from those that are responders, or simply secondary effects without further function. The
Upstream analysis of signal fingerprints – endometrial sensing
Large-scale transcriptome data may not only describe physiological changes that lead to downstream protein translation and function. They can also mirrow most valuable information regarding present events. This means that transcriptome expression differences can hold as fingerprints that allow the interpretation of stimuli that occur. The expression fingerprint is independent from further down-stream reactions that take place. Rather, the vast number of changes, that do not necessarily need to
Conclusion
In mammals, species-specific differences in mechanisms of embryo recognition and establishment of pregnancy hold major challenges in molecular recapitulation. However, by unraveling the difficulties, comparative analyses of endometrial gene expression offer great opportunities to find homologous changes and distinct differences to draw conclusions for further species including humans, where analyses are difficult to perform. Analysis of the endometrial transcriptome may not only increase the
Acknowledgements
Our studies were supported by the Deutsche Forschungsgemeinschaft (FOR478, FOR1029), the German Ministry for Education and Research (BMBF; programs FUGATO and FUGATO-plus; projects FERTILINK and COMPENDIUM) and in part by the Society for Reproduction and Fertility.
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