Transcriptome Analysis Reveals Transforming Growth Factor-β1 Prevents Extracellular Matrix Degradation and Cell Adhesion During the Follicular-luteal Transition in Cows

Ovarian angiogenesis is an extremely rapid process that occurs during the transition from follicle to corpus luteum (CL) and is crucial for reproduction. It is regulated by numerous factors including transforming growth factor-β1 (TGFB1). However, the regulatory mechanism of TGFB1 in ovarian angiogenesis is not fully understood. To address this, in this study we obtained high-throughput transcriptome analysis (RNA-seq) data from bovine luteinizing follicular cells cultured in a system mimicking angiogenesis and treated with TGFB1, and identified 455 differentially expressed genes (DEGs). Quantitative real-time PCR results confirmed the differential expression patterns of the 12 selected genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified that the MAPK and ErbB pathways, cell adhesion molecules (CAMs), and extracellular matrix (ECM)-receptor interactions may play pivotal roles in TGFB1-mediated inhibition of CL angiogenesis. TGFB1 phosphorylated ERK1/2 (MAPK1/3) and Akt, indicating that these pathways may play an important role in the regulation of angiogenesis. Several genes with specific functions in cell adhesion and ECM degradation were identified among the DEGs. In particular, TGFB1-induced upregulation of syndecan-1 (SDC1) and collagen type I alpha 1 chain (COL1A1) expression may contribute to the deposition of type I collagen in luteinizing follicular cells. These results indicate that TGFB1 inhibits cell adhesion and ECM degradation processes involving ERK1/2, ErbB, and PI3K/Akt signaling pathways, and leads to inhibition of angiogenesis during the follicular-luteal transition. Our results further reveal the molecular mechanisms underlying the actions of TGFB1 in early luteinization.