Multi-Platform Expression Analyses Reveal a Putative INHBA-SERPINE2-SDF2L1 Co-Regulated Module in the Bovine Cumulus–Oocyte Complex

Bidirectional communication between the oocyte and surrounding follicular cells coordinates follicle growth, meiotic maturation, and the acquisition of competence. We aimed to identify genes related to follicular crosstalk and the secretory pathway as candidate mediators of cumulus–oocyte complex (COC) crosstalk in cattle. Expressed sequence tags (ESTs) from bovine COCs were retrieved from databases and screened for genes related to secretion and the secretory pathway using SignalP and SecretomeP, and transmembrane proteins were removed, yielding 13 candidate genes. Candidate expression was examined in two GEO RNA-seq datasets to assess enrichment in oocytes versus cumulus cells. RT–qPCR profiling across tissues and reproductive cell types enabled principal component analysis and correlation/network analysis, visualized as heatmaps and Cytoscape, revealing an INBHA-SERPINE2-SDF2L1 co-expression pattern. INHBA and SERPINE2 protein products are secreted, whereas SDF2L1 protein is a secretory pathway-associated, endoplasmic reticulum-resident chaperone. Promoter sequences of INHBA, SERPINE2, and SDF2L1 were scanned with FIMO using JASPAR motifs, identifying shared SMAD-associated motifs and FSH/cAMP-related motif families. The data support a co-regulation model in which endocrine FSH/cAMP and activin/TGF-β–SMAD inputs converge on a shared transcriptional program consistent with a putative INHBA–SERPINE2–SDF2L1 co-regulated module, linking cumulus extracellular matrix remodeling/protease control with oocyte ER protein folding capacity during COC maturation.