Advances in the Molecular Regulatory Mechanisms of Testicular Development and Spermatogenesis in Yaks.

Yaks are indigenous livestock species of the Qinghai-Tibet Plateau. Due to long-term exposure to extreme environmental stressors, including high altitude, hypoxia, and low temperatures, its male reproductive system has evolved distinct adaptive strategies. Specifically, testicular weight is markedly lower than that of cattle. Nevertheless, according to reported data from different experiments, although its single ejaculate volume is lower than that of Tibetan cattle, it can still maintain comparable fresh sperm motility. These reproductive phenotypes make the yak an ideal model organism for investigating plateau adaptation and sperm energy metabolism. The present review synthesizes continuous molecular events in yak testes spanning embryonic development through senescence. It focuses on dissecting the core regulatory networks governing spermatogonial stem cell self-renewal, meiosis, and spermiogenesis. It integrates the latest advances in testicular microenvironment dynamics and epigenetic modifications. Additionally, male sterility in cattle-yak serves as a natural mutant model. Essential regulatory modules governing spermatogenesis can be inferred from its spermatogenic-arrest phenotype. Nevertheless, comparative omics analyses between yaks and cattle are confounded by seasonal variation and differing genetic backgrounds. It is therefore critical to distinguish signatures driven by genetic adaptation from those arising from environmental plasticity. Finally, this paper presents research prospects regarding how to utilize single-cell multi-omics and gene-editing technologies to deeply dissect the underlying mechanisms of plateau reproductive adaptation to provide theoretical support for improving yak fecundity and hybrid breeding.