Applications of large-scale molecular profiling techniques to the study of the corpus luteum

The corpus luteum (CL) is vital for the establishment and maintenance of pregnancy. Throughout the history of luteal biology, cutting-edge technologies have been used to develop a thorough understanding of the functions of specific luteal cell types, the signaling pathways that result in luteal cell stimulation or demise, and the molecules that regulate specific functions of luteal cells. The advent of large- scale profiling technologies such as transcriptomics, proteomics, and metabolomics, has brought with it an interest in discovering novel regulatory molecules that may provide targets for manipulation of luteal function or lifespan. Although the work to date is limited, transcriptomics have been effectively used to provide a global picture of changes in mRNA that relate to luteal development, steroidogenesis, luteolysis or luteal rescue. Some studies have been reported that profile microRNA (miRNA) and proteins, and although not yet published, metabolomics analyses of the CL have been undertaken. Thus far, these profiling studies seem to largely confirm earlier findings using targeted approaches, although previously unstudied molecules have also come to light as important luteal regulators. These molecules can then be studied using traditional mechanistic techniques. Use of profiling technologies has presented physiologists with unique challenges associated with analyses of big data sets. An appropriate technique for balancing the risks associated with type I (false discoveries) and type II (overlooking a real change) statistical error has not yet been developed and many big data studies may have potentially important differences that are overlooked. Also, it is imperative that attempts be made to integrate information from the various -omics studies before drawing conclusions based on expression of only one class of molecule, to better reflect the interdependency of molecular networks in cells. Currently, few analysis programs exist for such integrations. Despite challenges associated with these techniques, they have already provided new information about the biology of the CL, notably allowing identification of a key regulator of acquisition of luteolytic capacity and providing a big-picture view of the subtle changes that occur in the CL during early pregnancy. As these technologies become more accurate and less expensive, and as analysis becomes more user- friendly, their use will become much more widespread and many new discoveries will be made. This review will focus only on relevant studies in which these technologies were used to study the CL of ruminants.