A transcriptomic map of ligand-receptor interactions within bovine antral follicles reveals commonality and redundant strategies for intercellular communications and predicts intrafollicular factors for improving oocyte quality

Despite the importance, how these cell populations communicate remains largely unknown. Due to this knowledge gap, current oocyte in vitro maturation (IVM) systems fail to fully replicate the physiological follicular microenvironment due to the lack of MGC regulation, leading to poor oocyte quality and lower success rate of assisted reproductive technologies. Results: RNA-seq was performed on MGCs, CCs, and oocytes isolated from single bovine antral follicles at different developmental stages (3–5 mm, 6–8 mm and 9–12 mm). Using a ligand-receptor interaction scoring strategy, we constructed a dynamic intrafollicular interaction map. We revealed that MGCs are the most active cell type, acting as either secretors or receivers. Intriguingly, intrafollicular crosstalk utilizes a spatiotemporally degenerate strategy, characterized by extensive ligand-receptor redundancy across cell types and stages. Notably, the intrafollicular communication map enables the prediction of MGC-secreted factors that can improve the oocyte quality after IVM. Based on the predicted candidate factors, we have confirmed that supplementation with PTN significantly improved in vitro matured oocyte quality and subsequent embryonic development. In addition, we also revealed significant heterogeneity at single-follicle resolution, unhealthy follicles showed aberrant activation or loss of partial core interaction signaling, suggesting the critical role of interactions in determining follicular fate. Conclusions: By reconstructing a map of intrafollicular interaction map, our study provides novel insights and important clues for understanding cellular and molecular mechanisms that fine-tune antral folliculogenesis. We also offer a roadmap for predicting candidate factors that can be used for optimizing mammalian in vitro embryo production system.