Single-cell transcriptome analysis of Bisphenol A exposure reveals the key roles of the testicular microenvironment in male reproduction.

Testicular development during juvenile is crucial for subsequent male reproductive function. However, it remains poorly understood about the contribution of the testis microenvironment to human germ cell maturation. Therefore, we systematically analyzed scRNA-seq transcriptome and found the dramatic changes in cell-type composition in human testis during puberty. Then we constructed cell-cell communication networks between germ cells and somatic cells in the juvenile testis, which may be achieved via immune-related pathways. Our results showed that maturation-promoting factors are the switches of the Sertoli cells that drive sperm maturation. Furthermore, we found that Bisphenol A(BPA) enhanced the maturation and growth of germ cells through the Sertoli cell's secretory protein. Finally, our results indicate Bisphenol A would lead to the dysregulation of secreted protein expression in Sertoli cells during spermatogenesis, which in turn has direct cytotoxicity to Sertoli cells. Bisphenol A is one of the underlying causes of non-obstructive azoospermia (NOA). In summary, our results reveal the reproductive toxicity and molecular mechanism of Bisphenol A in Sertoli cells and male reproduction. Provide a reference for the toxicity of Bisphenol A to human reproduction.

Specific expression and alternative splicing of mouse genes during spermatogenesis.

Considering the high abundance of spliced RNAs in testis compared to other tissues, it is needed to construct the landscape of alternative splicing during spermatogenesis. However, there is still a lack of the systematic analysis of alternative RNA splicing in spermatogenesis. Here, we constructed a landscape of alternative RNA splicing during mouse spermatogenesis based on integrated RNA-seq data sets. Our results presented several novel alternatively spliced genes (Eif2s3y, Erdr1 Uty and Zfy1) in the Y chromosome with a specific expression pattern. Remarkably, the alternative splicing genes were grouped into co-expression networks involved in the microtubule cytoskeleton organization and post-transcriptional regulation of the gene expression, indicating the potential pathway to germ cell generation. Furthermore, based on the co-expression networks, we identified Atxn2l as a potential key gene in spermatogenesis, which presented dynamic expression patterns in different alternative splicing types. Ultimately, we proposed splicing regulatory networks for understanding novel and innovative alternative splicing regulation mechanisms during spermatogenesis. In summary, our research provides a systematic analysis of alternative RNA splicing and some novel spliced genes related to spermatogenesis.