Altered mRNAs Profiles in the Testis of Patients With "Secondary Idiopathic Non-Obstructive Azoospermia"

Dongdong Tang; Kuokuo Li; Mingrong Lv; Chuan Xu; Hao Geng; Chao Wang; Huiru Cheng; Xiaojin He; Yan Zhang; Yunxia Cao

doi:10.3389/fcell.2022.824596

Altered mRNAs Profiles in the Testis of Patients With "Secondary Idiopathic Non-Obstructive Azoospermia"

Front Cell Dev Biol. 2022 May 12:10:824596. doi: 10.3389/fcell.2022.824596. eCollection 2022.

Authors

Dongdong Tang^{1

2

3}, Kuokuo Li^{1

2

3}, Mingrong Lv^{1

2

3}, Chuan Xu¹, Hao Geng¹, Chao Wang¹, Huiru Cheng^{1

2

3}, Xiaojin He^{1

2

3}, Yan Zhang⁴, Yunxia Cao^{1

2

3}

Affiliations

¹ Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
² NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, China.
³ Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Hefei, China.
⁴ Department of Clinical Laboratory, Renmin Hospital of Wuhan University, WuHan, China.

Abstract

Background: Non-obstructive azoospermia (NOA) is the most severe form of male infertility. Currently, known causative factors, including congenital and several acquired causes only account for approximately 30% of NOA cases. The causes for NOA remain unclear for most patients, which is known as idiopathic (iNOA). However, whether iNOA is due to congenital defects or acquired abnormalities is a confusing problem due to the delayed diagnosis of this frustrating condition until the childbearing age. Therefore, we collected several cases with "secondary idiopathic NOA" and detected the altered mRNAs profiles in the testicular tissues to explore the possible molecular basis. Materials and Methods: In this study, several patients with a previous history of natural pregnancy with their partners before, who were diagnosed as iNOA based on the outcomes of routine semen analysis and multiple testis biopsies now, were enrolled. Some known risk factors and genetic factors were excluded. Therefore, we defined this phenotype as "secondary idiopathic NOA." To explore the possible molecular basis of this disease, we performed mRNA expression analysis through next-generation sequencing on three cases and other three patients with obstructive azoospermia as controls. Bioinformatics analyses were conducted to assess differentially expressed genes and possible biological mechanisms involved in the disease. Quantitative real-time reverse transcription polymerase chain reaction assays were applied to confirm the results in several selected mRNAs involved in stages and metabolism of Sertoli cells. Results: A series of mRNAs were found to be altered in testicular tissues between patients with "secondary idiopathic NOA" and controls, including 6,028 downregulated and 3,402 upregulated mRNAs. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses revealed a range of GO and KEGG terms, such as cellular process involved in reproduction, protein degradation, and absorption. Conclusion: The present study introduces a novel classification called "secondary idiopathic NOA." We provide a global view of the altered mRNAs involved in spermatogenetic failure in these cases. Regarding the limited samples, further studies should be taken to understand this new classification.

Keywords: idiopathic; mRNA; non-obstructive azoospermia; profile; secondary.