Elsevier

Methods

Volume 59, Issue 1, January 2013, Pages 108-115
Methods

Review Article
Transcriptional profiling to address molecular determinants of endometrial receptivity – Lessons from studies in livestock species

https://doi.org/10.1016/j.ymeth.2012.10.013Get rights and content

Abstract

The development of a fertilized oocyte into a differentiated multi-cellular organism is a major challenge with regard to the orchestration of the expression of the mammalian genome. Highly complex networks of genes are temporally and spatially regulated during cellular differentiation to generate specific cell types. Embryonic development is critically influenced by external impacts in the female reproductive tract. A most critical phase of pregnancy in mammals is the pre- and peri-implantation period, during which the uterine environment plays a crucial role in supporting the development of the conceptus. The analytical description of the transcriptome, proteome and metabolome of the embryo-maternal interface is a prerequisite for the understanding of the complex regulatory processes taking place during this time. This review lines out potentials and limitations of different approaches to unravel the determinants of endometrial receptivity in cattle, the pig and the horse. Suitable in vivo and in vitro models, which have been used to elucidate factors participating in the embryo-maternal dialog are discussed. Taken together, transcriptome analyses and specified selective candidate gene driven approaches contribute to the understanding of endometrial function. The endometrium as sensor and driver of fertility may indicate the qualitative and quantitative nature of signaling molecules sent by the early embryo and in turn, accordingly impact on embryonic development.

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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