Background: Non-obstructive azoospermia (NOA) is considered one of the most severe forms of male infertility. Despite the limited range of testicular phenotypes, NOA exhibits considerable genetic heterogeneity. The aim of this study was to uncover the etiopathogenesis of NOA and provide insights into the outcomes of testicular sperm extraction (TESE).
Material Method: To elucidate the potential causes of testicular pathogenesis, a cohort of 61 patients was analyzed. The genetic etiology was assessed using our developed gene panel, based on genes with prior functional studies conducted specifically in the context of testicular characterization.
Results: Our analytical approach, built upon these findings, enabled us to explore the potential genetic causes of NOA and assess their relevance to TESE outcomes. A potential causal defect was identified in 14 genes across a total of 26 individuals (42%). Of these, three genes-MEIOB, TERB1, and USP26-had been previously described in men, while eight genes-SPO11, RBBP7, STS, RBMXL3, ZCCHC13, HUWE1, ESR1, and ABCD1-had been reported in prior studies. Additionally, three genes-CEP85, NAP1L3, and CENPI-had been previously described only in knockout (KO) phenotype studies, and this study represents the first identification of these genes in men.
Conclusion: Interestingly, the histological findings of meiotic arrest were strongly linked to genes involved in meiosis, reinforcing the clinical diagnosis of patients in this cohort. Additionally, our study underscores the importance of refining diagnostic strategies that focus on genes associated with testicular phenotypes, which could enhance the accuracy of TESE success predictions.
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http://dx.doi.org/10.1007/s10815-025-03409-5 | DOI Listing |
J Assist Reprod Genet
March 2025
Department of Reproductive Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, Jiangsu, China.
Purpose: We aimed to demonstrate the genetic factors of primary gonadal dysgenesis in a consanguineous family characterized by underdeveloped testes and non-obstructive azoospermia (NOA) in a male and primary amenorrhoea and primary ovarian insufficiency (POI) in a female.
Methods: DNA was extracted from the male proband with infertility from the consanguineous family for whole-exome sequencing and bioinformatics analysis to screen for potential pathogenic genes and mutations. Sanger sequencing was used for further validation of his family pedigree.
Hum Reprod
March 2025
Department of Growth and Reproduction, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Study Question: Is semen quality associated with the lifespan of men?
Summary Answer: Men with a total motile sperm count of >120 million could expect to live 2.7 years longer than men with total motile sperm count of >0-5 million.
What Is Known Already: Male infertility and semen quality have been suggested to be markers of morbidity and thus mortality, but the role of underlying disease present at time of semen quality evaluation has not been thoroughly assessed.
Front Endocrinol (Lausanne)
March 2025
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China.
Background: RNA-binding proteins (RBPs) have emerged as key regulators in testis development and spermatogenesis, yet a comprehensive understanding of their expression dynamics has been lacking.
Methods: This study leverages published single-cell RNA sequencing (scRNA-seq) data to elucidate the complex expression patterns of RBP genes during postnatal testis development and spermatogenesis. Additionally, it uses bulk RNA-seq data to explore the regulatory impact of RBPs on alternative splicing (AS) in non-obstructive azoospermia (NOA).
Steroids
February 2025
School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255000, China; School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, Shandong 266113, China. Electronic address:
Non-obstructive azoospermia (NOA) is the most common cause of male infertility, accounting for approximately 60 % of azoospermia cases. In recent years, gene mutations have emerged as the primary factor under investigation for the etiology of NOA. Therefore, finding the cause and pathogenesis of NOA at the genetic level has become one of the current research hotspots.
View Article and Find Full Text PDFCell Mol Life Sci
February 2025
Department of Obstetrics and Gynecology, Perinatal Medical Center, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52 Meihua East Road, Zhuhai, Guangdong, People's Republic of China.
Bcl-2 associated athanogene-5 (BAG5) represents a unique BAG cochaperone family member, regulating chaperone activity. We first demonstrated significant differences in Bag5 expression by RNA seq analysis of teratozoospermia and healthy male sperm samples, but the genetic and molecular mechanisms governing this process remain elusive. We further found that BAG5 has highest expression in human and mouse testes.
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