Single‐cell RNA sequencing of the Mongolia sheep testis reveals a conserved and divergent transcriptome landscape of mammalian spermatogenesis

Abstract

Spermatogenesis is a highly coordinated and complex process, and is pivotal for transmitting genetic information between mammalian generations. In this study, we investigated the conservation, differences, and biological functions of homologous genes during spermatogenesis in Mongolia sheep, humans, cynomolgus monkey, and mice using single-cell RNA sequencing technology. We compared X chromosome meiotic inactivation events in Mongolia sheep, humans, cynomolgus monkey, and mice to uncover the concerted activity of X chromosome genes. Subsequently, we focused on the dynamics of gene expression, key biological functions, and signaling pathways at various stages of spermatogenesis in Mongolia sheep and humans. Additionally, the ligand-receptor networks of Mongolia sheep and humans in testicular somatic and germ cells at different developmental stages were mapped to reveal conserved germ cell-soma communication using single-cell resolution. These datasets provided novel information and insights to unravel the molecular regulatory mechanisms of Mongolia sheep spermatogenesis and highlight conservation in gene expression during spermatogenesis between Mongolia sheep and humans, providing a foundation for the establishment of a large mammalian disease model of male infertility.

Application of single-cell RNA sequencing on human testicular samples: a comprehensive review

“…Another important type of re-analyses of human testicular scRNA-seq data is to do species or sex comparisons. For species comparison, so far, the spermatogenesis of mouse 165 , mouse lemur 165 , chicken 166 , cynomolgus macaque 167 , sheep 168 and the somatic development of pigs 169 has been fully compared with that of human. The similarities of these studies were that they reported both conserved (especially the conservatism of X chromosome inactivation) and species-specific features among different animals and human.…”

“…The similarities of these studies were that they reported both conserved (especially the conservatism of X chromosome inactivation) and species-specific features among different animals and human. A good example would be Tian et al's work, in which they compared the spermatogenesis of four different species (human, mouse, sheep and cynomolgus macaque) 168 . In that study, they found the spermatogenesis between sheep and human were partially conserved at the transcriptional level (e.g., similar regulators were expressed in the same stages of spermatogenesis in human and sheep) and further showed the high conservatism of X chromosome inactivation during meiosis among four species 168 , which was in line with Lau et al's report 167 .…”

“…A good example would be Tian et al's work, in which they compared the spermatogenesis of four different species (human, mouse, sheep and cynomolgus macaque) 168 . In that study, they found the spermatogenesis between sheep and human were partially conserved at the transcriptional level (e.g., similar regulators were expressed in the same stages of spermatogenesis in human and sheep) and further showed the high conservatism of X chromosome inactivation during meiosis among four species 168 , which was in line with Lau et al's report 167 . On the other hand, Rengaraj et al reported a large proportion of species-specific genes between human and chickens (24 out of 56 orthologs) during the development of male fetal germ cells 166 .…”

Whole genome re-sequencing reveals artificial and natural selection for milk traits in East Friesian sheep

“…The candidate genes B4GALNT4 ( 33 ) involved in lactose synthesis, RCOR1 ( 34 ) related to milk yield and SH3D19 related to lactation process in sheep were also identified ( 35 ). In addition, our results contain a large number of candidate genes related to production traits, such as reproductive trait candidates: FSIP2 ( 17 ), CD226 ( 36 ), SLC44A5 ( 37 ), GPR83 ( 38 ), SUN5 ( 39 ), GPR173 ( 40 ), LHX8 ( 41 ), SIRT3 ( 42 ), FGF16 ( 43 ), POU3F4 ( 44 ), these genes affect reproductive traits by influencing days of estrus, luteal gland, participating in reproductive regulation, and hypothalamic-pituitary-gonadal axis regulation. For example, the candidate genes for wool traits: RALY ( 45 ), GLI2 ( 46 ), TXNRD3 ( 47 ), EIF2S2 ( 45 ), IRF2BP2 ( 48 ), etc.…”

Integrated single cell transcriptome sequencing analysis reveals species‐specific genes and molecular pathways for pig spermiogenesis

“…In farm animals, testicular scRNA‐seq studies have been performed on sheep (Tian et al., 2022; Yang et al., 2021), goat (Ren et al., 2022), buffalo (Huang et al., 2022), and yak (Wang, Pei, et al., 2023). In pigs, male germ cells and somatic cells (3 types) were defined first on the mature testis of a Chinese local pig breed (Zhang et al., 2021).…”