Orchestrating homolog segregation in meiosis I: molecular logic and regulatory networks with emphasis on male metaphase I

Accurate segregation of homologous chromosomes during meiosis I (MI) is essential for haploid gamete production. This review systematically summarizes the dynamic regulatory mechanisms governing chromosome segregation in male mammalian meiosis. During prophase I, crossover-dependent connections are established through DNA double-strand break repair, synaptonemal complex assembly, and sister chromatid cohesion—prerequisites for stable bivalent formation. At metaphase I, the spindle assembly checkpoint monitors kinetochore-microtubule attachments, while Aurora B kinase and the chromosomal passenger complex regulate attachment stability and error correction. Polo-like kinase 1 (PLK1) coordinates spindle assembly, whereas the anaphase-promoting complex/cyclosome drives the metaphase-to-anaphase transition, through targeted degradation of securin and cyclin B1. The Rec8-containing cohesin complex resists separase-mediated cleavage until anaphase I, thereby preserving sister chromatid cohesion until meiosis II. However, current knowledge of the regulatory mechanisms governing homologous chromosome segregation during male meiosis remains fragmented and has not been systematically integrated. Therefore, this review compares the mechanisms of chromosome segregation in male meiosis with those in mitosis and female meiosis in order to highlight both shared features and male-specific molecular mechanisms, and provides a systematic framework for understanding the separation of homologous chromosomes during male meiosis I.