Research

February 02, 2026

Dynamic regulation of spermatogenesis and hybrid sterility revealed by single-cell analysis in yak and cattle

Spermatogenesis is a highly orchestrated germ cell differentiation process involving the dynamic regulation of cell fate transitions. Dissecting the molecular landscapes of spermatogenic cell types is crucial for identifying fertility-related problems and improving the reproductive performance of farm animals. Here, we conducted transcriptomic and chromosome spreading across meiotic stages of testicular cells from taurine cattle (Bos taurus), yak (Bos grunniens) and their hybrid progenies to describe the transcriptional landscape of normal spermatogenesis and identify potential regulators that are involved in hybrid sterility. The results revealed 7 types of spermatogonia, 10 spermatocytes and 10 types of spermatids in the cattle or yak testes. In sharp contrast, the testes of the cattle–yak hybrids contained only 7 spermatogonial subtypes and 6 types of spermatocytes. Notably, the arrest of spermatocytes at the diplotene-to-diakinesis transition was accompanied by defects in double-strand break (DSB) repair. In the testes of backcrossed offspring, spermatogenic arrest was partially rescued, and round spermatozoa were produced. By performing joint analysis, we identified 115 genes that exhibited differential protein abundance in spermatocytes of cattle-yak. Among them, 24 genes carrying genomic structural variations (SVs) were differentially expressed in spermatocytes of cattle-yak but recovered in those of backcrossed offspring. This work provides important insights into spermatogenesis in large animals and serves as a valuable resource for identifying the factors determining reproductive isolation.

Fig. 9. Screening of DEGs with structural variants in various germ subtypes of cattle, yak, cattle-yak and BC1. The results were obtained by using the yak and taurine cattle reference genomes for cattle–yak and BC1. A) Histogram showing the number of upregulated and downregulated genes in cattle-yak but recovered in BC1,with structural variants in various subpopulations of spermatogonia and spermatocytes. B) Schematic diagram of the violin plots and structural variants of representative genes.C) Histogram showing the number of DEGs with structural variants in various spermatid subtypes of BC1 compared with yak and cattle. D) Venn diagrams and GO enrichment analysis of all DEGs with restored expression levels in spermatocytes of BC1 and differentially abundant proteins (DAPs) in spermatocytes of cattle-yak. E) Venn diagrams of all recovered DEGs. SVs in spermatocytes of BC1 and all DAPs in spermatocytes of cattle-yak. DAPS: differentially abundant proteins.

The link below will guide you to the reading:

https://doi.org/10.1093/molbev/msag027