Human obstructive (postvasectomy) and nonobstructive azoospermia - Insights from scRNA-Seq and transcriptome analysis

Shitao Chen; Geng An; Hanshu Wang; Xiaolong Wu; Ping Ping; Longfei Hu; Yunmei Chen; Jue Fan; C Yan Cheng; Fei Sun

doi:10.1016/j.gendis.2020.09.004

Human obstructive (postvasectomy) and nonobstructive azoospermia - Insights from scRNA-Seq and transcriptome analysis

Genes Dis. 2020 Sep 28;9(3):766-776. doi: 10.1016/j.gendis.2020.09.004. eCollection 2022 May.

Authors

Shitao Chen¹, Geng An², Hanshu Wang¹, Xiaolong Wu³, Ping Ping⁴, Longfei Hu⁵, Yunmei Chen⁵, Jue Fan⁵, C Yan Cheng⁶, Fei Sun^{1

3}

Affiliations

¹ International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, PR China.
² Department of Reproductive Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, PR China.
³ Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu 226001, PR China.
⁴ Department of Urology, Shanghai Human Sperm Bank, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200120, PR China.
⁵ Singleron Biotechnologies Ltd, Nanjing, Jiangsu 210000, PR China.
⁶ The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, NY 10065, USA.

Abstract

A substantial number of male infertility is caused by azoospermia. However, the underlying etiology and the molecular basis remain largely unknown. Through single-cell (sc)RNA sequencing, we had analyzed testis biopsy samples from two patients with obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). We found only somatic cells in the NOA samples and explored the transcriptional changes in Sertoli cells in response to a loss of interactions with germ cells. Moreover, we observed a germ cell population discrepancy between an OA (postvasectomy) patient and a healthy individual. We confirmed this observation in a secondary study with two datasets at GSM3526588 and GSE124263 for detailed analysis wherein the regulatory mechanisms at the transcriptional level were identified. These findings thus provide valuable information on human spermatogenesis, and we also identified insightful information for further research on reproduction-related diseases.

Keywords: Androgen signaling; Retinoic acid; Sertoli cell-only syndrome; Single-cell; Spermatogenesis.