Applications of Single-Cell Genomics to Infertility: A Review

Introduction: A large percentage of people worldwide suffer from infertility, a growing public health issue. However, the complex underlying causes of infertility are often overlooked. Recent advances in single-cell genomics have provided a powerful approach for understanding cellular heterogeneity and molecular mechanisms in reproductive tissues, offering significant improvements over traditional bulk analyses. Methods: This review summarizes the application of single-cell RNA sequencing (scRNA-seq) and other single-cell genomic techniques to the study of infertility. It critically evaluates the main methods for isolating single cells, including FACS, MACS, LCM, micromanipulation, and microfluidics. Key bioinformatics tools used for data analysis and interpretation are also discussed. Results: Recent studies have demonstrated the capacity of single-cell technologies to reveal previously undetected cell types and pathways involved in ovarian and testicular development. These technologies have provided new insights into the causes of male, female, and mixed infertility and the influence of endocrine disruptors on reproductive tissues. Discussion: The review highlights the transformative potential of single-cell genomics to advance our understanding of the biology of reproduction. These technologies enable precise characterization of reproductive cells and tissues at single-cell resolution, supporting the development of novel diagnostics and therapeutic strategies. Conclusion: Single-cell genomics provides a new framework for investigating infertility by enabling detailed interrogation of complex reproductive systems. This review outlines both the opportunities and limitations of these approaches and emphasizes their value in studying ovarian and testicular function.