Single-Cell Transcriptomics-Based Study of Transcriptional Regulatory Features in the Non-Obstructive Azoospermia Testis

Xiao-Juan Tang; Qiao-Hong Xiao; Xue-Lin Wang; Yan He; Ya-Nan Tian; Bin-Tong Xia; Yang Guo; Jiao-Long Huang; Peng Duan; Yan Tan

doi:10.3389/fgene.2022.875762

Single-Cell Transcriptomics-Based Study of Transcriptional Regulatory Features in the Non-Obstructive Azoospermia Testis

Front Genet. 2022 May 20:13:875762. doi: 10.3389/fgene.2022.875762. eCollection 2022.

Authors

Xiao-Juan Tang^{1

2}, Qiao-Hong Xiao², Xue-Lin Wang², Yan He^{2

3}, Ya-Nan Tian^{2

3}, Bin-Tong Xia⁴, Yang Guo², Jiao-Long Huang², Peng Duan², Yan Tan^{1

5

6}

Affiliations

¹ Department of Andrology, Renmin Hospital, Hubei University of Medicine, Shiyan, China.
² Key Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Xiangyang City, Department of Obstetrics and Gynaecology, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
³ Postgraduate Training Basement of Jinzhou Medicical University, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
⁴ Department of Urology Surgery, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
⁵ Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China.
⁶ Biomedical Engineering College, Hubei University of Medicine, Shiyan, China.

Abstract

Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. Although many congenital factors have been identified, the aetiology in the majority of idiopathic NOA (iNOA) cases remains unknown. Herein, using single-cell RNA-Seq data sets (GSE149512) from the Gene Expression Omnibus (GEO) database, we constructed transcriptional regulatory networks (TRNs) to explain the mutual regulatory relationship and the causal relationship between transcription factors (TFs). We defined 10 testicular cell types by their marker genes and found that the proportion of Leydig cells (LCs) and macrophages (tMΦ) was significantly increased in iNOA testis. We identified specific TFs including LHX9, KLF8, KLF4, ARID5B and RXRG in iNOA LCs. In addition, we found specific TFs in iNOA tMΦ such as POU2F2, SPIB IRF5, CEBPA, ELK4 and KLF6. All these identified TFs are strongly engaged in cellular fate, function and homeostasis of the microenvironment. Changes in the activity of the above-mentioned TFs might affect the function of LCs and tMΦ and ultimately cause spermatogenesis failure. This study illustrate that these TFs play important regulatory roles in the occurrence and development of NOA.

Keywords: leydig cells; non-obstructive azoospermia; spermatogenesis; testicular macrophages; transcription factors.