Major Histocompatibility Complex Genomic Regions as Candidates for Reproductive Success in Cattle: From GWAS to Post-GWAS Analysis

Background: The major histocompatibility complex (MHC) is a well-known gene complex that plays a fundamental role in immune recognition; however, its influence on reproductive processes in cattle is not yet fully established, particularly regarding how it modulates the female response to the embryo. Therefore, this study aimed to investigate the relationship between MHC genes and reproductive processes in cattle and to identify potential molecular targets involved in these mechanisms. Methods: Data from four studies identified through a systematic review were integrated. MHC genes associated with reproduction were identified, neighboring genomic regions were explored to detect candidate genes and transcription factors, and biological process networks were constructed using differentially expressed genes associated with cattle. Results: The integrated analysis led to the identification of six MHC genes associated with reproduction, along with 54 candidate genes from genome-wide association studies and 46 from transcriptomic studies located in neighboring regions. Among these, BoLA-DQB and BoLA-DQA5 stood out in all analyses, while the transcription factors FOXA1, FOXO3, ELF5, and STAT3 appeared across the different datasets. These genes and factors may represent potential targets for future functional validations and could be explored using genome editing technologies to better understand their roles in reproductive processes. The identified biological pathways were related to embryonic development and reproductive organ formation, providing a preliminary foundation for future investigations. Conclusions: This work integrates currently available evidence and highlights potential molecular targets that can be explored in cattle breeding and reproductive biology, associating MHC genes with these roles and advancing innovative perspectives in the field of molecular genetics.