Identification of PDCL2 as a candidate marker in Sertoli cell-only syndrome by chromatin immunoprecipitation-sequencing and bioinformatics analysis

Yu Yang; Si Qin; Hongwei Wu; Jiahao Zhang; Qiao Tian; Zhengping Zhao; Benlin Wei; Jorge Hallak; Xiangming Mao

doi:10.21037/tau-23-304

Identification of PDCL2 as a candidate marker in Sertoli cell-only syndrome by chromatin immunoprecipitation-sequencing and bioinformatics analysis

Transl Androl Urol. 2023 Jul 31;12(7):1127-1136. doi: 10.21037/tau-23-304. Epub 2023 Jul 21.

Authors

Yu Yang^#^{1

2}, Si Qin^#^{3

4}, Hongwei Wu^#⁵, Jiahao Zhang⁶, Qiao Tian², Zhengping Zhao², Benlin Wei², Jorge Hallak^{7

8

9

10}, Xiangming Mao¹

Affiliations

¹ Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
² Department of Urology, Peking University Shenzhen Hospital, Shenzhen, China.
³ Department of Dermatology, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
⁴ Department of Dermatology, Guangdong Second Provincial General Hospital, Guangzhou, China.
⁵ Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
⁶ Department of Urology, Shenzhen Baoan People's Hospital (Group), Shenzhen, China.
⁷ Androscience, Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Research Laboratory, Sao Paulo, Brazil.
⁸ Division of Urology, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil.
⁹ Reproductive Toxicology Unit, Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil.
¹⁰ Institute of Advanced Studies, University of Sao Paulo, Sao Paulo, Brazil.

^# Contributed equally.

Abstract

Background: Sertoli cell-only syndrome (SCOS) or germ cell aplasia is one of the most serious histopathological subtypes within the scope of non-obstructive azoospermia (NOA). Understanding the molecular mechanism of SCOS and identifying new non-invasive markers for clinical application is crucial to guide proper sperm procurement and avoid unnecessary interventions. This study sought to identify the differentially expressed genes (DEGs) of SCOS by using gene sequencing identity and verify the key marker genes to provide basic data for subsequent research on SCOS.

Methods: A total of 50 testicular samples were collected in this study from 25 patients with SCOS and 25 patients with normal spermatogenesis. In total, 5 pairs of testis samples were used for the RNA-sequencing (RNA-seq). We identified the DEGs between the SCOS and normal spermatogenesis patients and conducted a Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The expression of the main target gene phosducin-like 2 (PDCL2) was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC).

Results: In total, 3,133 upregulated DEGs and 1,406 downregulated DEGs were identified by the RNA-seq. The highly enriched processes involved in spermatogenesis included the mitotic cell cycle, cell cycle, and oocyte maturation. The expression of PDCL2 was verified as a downregulation marker in SCOS by qRT-PCR and IHC.

Conclusions: This study identified the DEGs of SCOS, and the bioinformatics analysis results identified the potential target key genes and pathways for SCOS. PDCL2 is a key gene involved in SCOS and may serve as a non-invasive downregulation marker of SCOS.

Keywords: Non-obstructive azoospermia (NOA); Sertoli cell-only syndrome (SCOS); gene sequencing; phosducin-like 2 (PDCL2).