Proteomic profiling reveals potential mechanisms regulating acquisition of luteolytic capacity in the bovine corpus luteum

The corpus luteum (CL) produces progesterone to support pregnancy but undergoes luteolysis in response to prostaglandin F2A (PGF2A) when pregnancy is absent. Developing CL resist PGF2A-induced regression. This acquisition of luteolytic capacity (ALC) occurs around day 5 of the estrous cycle in cattle. To understand the mechanisms underlying ALC, we evaluated transcriptomic and proteomic changes in the CL on days 4 and 6 of the estrous cycle. 1190 transcripts were greater on day 4 and 119 were greater on day 6 (Padj <0.05, log2FC > |1|). In the proteomics dataset, 2 proteins were greater on day 4, with 12 greater on day 6 (Padj <0.05, log2FC > |1|). Data were integrated with datasets of luteal changes during luteolysis and during early pregnancy, and gene ontology analysis was used to identify candidate pathways regulating luteal PGF2A responsiveness, including apoptosis, cellular stress response, and cytokine signaling. Apoptosis regulators increased on day 6 and increased in response to PGF2A in vivo, indicating a likely role in luteolytic cell death. Changes to regulators of antigen presentation and T cell programming suggested increased T cell activation on day 6. A luteal cell culture experiment revealed that apoptosis pathways were regulated by interferon gamma and immune pathways were regulated by luteinizing hormone in vitro. In summary, integration across datasets from multiple luteal states allowed identification of proposed mediators governing luteal survival and PGF2A response. Apoptosis and immune-related pathways, changes indicating increased activated T cells, may poise the CL to regress in response to PGF2A.