Review
Cell Biology
Saffet Ozturk
Summary: Spermatogenic arrest in non-obstructive azoospermia (NOA) involves interruption of spermatogenesis at different stages, which has been investigated through genome/exome sequencing to identify genetic variants. Variants in genes related to mitosis, meiosis, germline differentiation, and cellular events have been discovered. This review comprehensively discusses defined variants in NOA cases with spermatogenic arrest and the creation of knockout mouse models for related genes, as well as emphasizes the importance of gene panel-based screening for NOA cases.
Review
Medicine, General & Internal
Caroline Kang, Nahid Punjani, Peter N. Schlegel
Summary: Non-obstructive azoospermia (NOA) is the most severe form of infertility, caused by spermatogenic dysfunction leading to lack of sperm in the ejaculate. Men with this condition should be evaluated before treatment to determine underlying causes. Despite the various etiologies, most NOA patients are suitable candidates for surgical sperm retrieval and ICSI treatment.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Genetics & Heredity
Jimmaline J. Hardy, Margot J. Wyrwoll, William Mcfadden, Agnieszka Malcher, Nadja Rotte, Nijole C. Pollock, Sarah Munyoki, Maria V. Veroli, Brendan J. Houston, Miguel J. Xavier, Laura Kasak, Margus Punab, Maris Laan, Sabine Kliesch, Peter Schlegel, Thomas Jaffe, Kathleen Hwang, Josip Vukina, Miguel A. Brieno-Enriquez, Kyle Orwig, Judith Yanowitz, Michael Buszczak, Joris A. Veltman, Manon Oud, Liina Nagirnaja, Marta Olszewska, Moira K. O'Bryan, Donald F. Conrad, Maciej Kurpisz, Frank Tuettelmann, Alexander N. Yatsenko
Summary: Male infertility impacts millions of couples, with the etiology largely unknown. A genomic study on spermatogenic failure identified potentially significant single-nucleotide variants in the GCNA gene. These variants disrupt protein domains critical for genome integrity, potentially causing germ-cell division arrest.
Article
Obstetrics & Gynecology
Ozlem Okutman, Manon Boivin, Jean Muller, Nicolas Charlet-Berguerand, Stephane Viville
Summary: By analyzing a large Turkish consanguineous family using whole exome sequencing, a homozygous nonsense variant in HORMAD1 was identified in three affected brothers with nonobstructive azoospermia (NOA). This study contributes to the understanding of the genetic causes of male infertility.
HUMAN REPRODUCTION
(2023)
Article
Genetics & Heredity
Sidra Qureshi, Jimmaline J. Hardy, Christopher Pombar, Andrea J. Berman, Agnieszka Malcher, Tara Gingrich, Rachel Hvasta, Jannah Kuong, Sarah Munyoki, Kathleen Hwang, Kyle E. Orwig, Jawad Ahmed, Marta Olszewska, Maciej Kurpisz, Donald F. Conrad, Muhammad Jaseem Khan, Alexander N. Yatsenko
Summary: Human spermatogenesis is a complex process that involves thousands of testis-specific genes. Defects in these genes can have detrimental effects on sperm production. This study identified and reported novel variants in the testis-expressed gene 15 (TEX15) that are associated with spermatogenic failure. The study also found a high frequency of TEX15 variants in patients with spermatogenic failure.
FRONTIERS IN GENETICS
(2023)
Article
Health Care Sciences & Services
Miriam Cervan-Martin, Lara Bossini-Castillo, Rocio Rivera-Egea, Nicolas Garrido, Saturnino Lujan, Gema Romeu, Samuel Santos-Ribeiro, Jose A. Castilla, M. Carmen Gonzalvo, Ana Clavero, F. Javier Vicente, Andrea Guzman-Jimenez, Claudia Costa, Ines Llinares-Burguet, Chiranan Khantham, Miguel Burgos, Francisco J. Barrionuevo, Rafael Jimenez, Josvany Sanchez-Curbelo, Olga Lopez-Rodrigo, M. Fernanda Peraza, Iris Pereira-Caetano, Patricia I. Marques, Filipa Carvalho, Alberto Barros, Lluis Bassas, Susana Seixas, Joao Goncalves, Sara Larriba, Alexandra M. Lopes, Rogelio J. Palomino-Morales, F. David Carmona
Summary: The study identified a significant difference in allele frequencies of USP8-rs7174015 between the NOA group, the control group, and the SO group, suggesting a possible association of this gene with male infertility. Other genetic associations were found for EPSTI1-rs12870438 and PSAT1-rs7867029 with SO, as well as TUSC1-rs10966811 with TESE success in the context of non-obstructive azoospermia.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Biology
Daria Adamczewska, Jolanta Slowikowska-Hilczer, Renata Walczak-Jedrzejowska
Summary: Leydig cells, located in the interstitial compartment of the testicle, play a vital role in male reproductive tract development and spermatogenesis. Dysfunction of these cells can lead to various testicular pathologies, including spermatogenic failure. This review provides an overview of the current knowledge on Leydig cells and focuses on their contribution to impairments in spermatogenesis.
Article
Obstetrics & Gynecology
Yang Li, Yufan Wu, Jianteng Zhou, Huan Zhang, Yuanwei Zhang, Hui Ma, Xiaohua Jiang, Qinghua Shi
Summary: Mutations in the ZSWIM7 gene, particularly the homozygous frameshift mutation (c.231_232del), may lead to male infertility by affecting meiotic recombination processes. This study provides direct clinical evidence of the correlation between ZSWIM7 mutations and male infertility.
HUMAN REPRODUCTION
(2021)
Article
Obstetrics & Gynecology
M. J. Wyrwoll, E. S. van Walree, G. Hamer, N. Rotte, M. M. Motazacker, H. Meijers-Heijboer, M. Alders, A. Meissner, E. Kaminsky, M. Woeste, C. Krallmann, S. Kliesch, T. J. Hunt, A. T. Clark, S. Silber, B. Stallmeyer, C. Friedrich, A. M. M. van Pelt, I. B. Mathijssen, F. Tuettelmann
Summary: The study identified bi-allelic variants in MSH4 and MSH5 as causes of male infertility, expanding the understanding of genetic factors contributing to azoospermia.
HUMAN REPRODUCTION
(2022)
Article
Urology & Nephrology
Adem Utlu, Fatih Ozkaya, Tugay Aksakalli, Ahmet Emre Cinislioglu, Saban Oguz Demirdogen, Mehmet Sefa Altay, Ibrahim Karabulut, Isa Ozbey, Sibel Guclu Utlu
Summary: This study compared the sperm retrieval rates between unilateral and bilateral microdissection testicular sperm extraction (MD-TESE) procedures in patients with non-obstructive azoospermia (NOA), and compared them with literature data. The results showed no significant difference in terms of sperm availability between the two groups of patients. Considering the operative time and complication rates of bilateral MD-TESE in patients with NOA, as well as possible subsequent MD-TESE procedures, unilateral MD-TESE is considered to be more preferable for this patient group.
INTERNATIONAL UROLOGY AND NEPHROLOGY
(2023)
Article
Genetics & Heredity
Zhiyong Ji, Chencheng Yao, Chao Yang, Chuan Huang, Liangyu Zhao, Xia Han, Zijue Zhu, Erlei Zhi, Nachuan Liu, Zhi Zhou, Zheng Li
Summary: In a study involving 479 NOA patients, 7 individuals (1.5%) were found to carry TEX11 gene mutations. Three novel mutations were identified in siblings from three families, and four novel mutations were identified in sporadic NOA-affected cases. These mutations were associated with meiotic arrest and predicted to be pathogenic.
FRONTIERS IN GENETICS
(2021)
Article
Developmental Biology
Weili Wang, Lanlan Meng, Jiaxin He, Lilan Su, Yong Li, Chen Tan, Xilin Xu, Hongchuan Nie, Huan Zhang, Juan Du, Guangxiu Lu, Mengcheng Luo, Ge Lin, Chaofeng Tu, Yue-Qiu Tan
Summary: Meiosis is a crucial process for gametogenesis and fertility, and meiotic recombination plays a significant role in ensuring accurate chromosome segregation and generating genetic diversity. Researchers have discovered that SHOC1 gene mutations have a strong clinical relevance to patients with non-obstructive azoospermia (NOA), shedding light on the mechanistic understanding of SHOC1 during meiotic recombination.
MOLECULAR HUMAN REPRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Chenjia Gong, Tanveer Abbas, Zubair Muhammad, Jianteng Zhou, Ranjha Khan, Hui Ma, Huan Zhang, Qinghua Shi, Baolu Shi
Summary: The MSH5 c.1126del mutation may cause meiotic recombination failure and infertility in humans. The study of human spermatocytes also reveals the importance of MutS γ in synapsis and meiotic recombination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Andrology
Miriam Cervan-Martin, Lara Bossini-Castillo, Rocio Rivera-Egea, Nicolas Garrido, Saturnino Lujan, Gema Romeu, Samuel Santos-Ribeiro, Jose A. Castilla, Maria del Carmen Gonzalvo, Ana Clavero, Francisco Javier Vicente, Andrea Guzman-Jimenez, Miguel Burgos, Francisco Javier Barrionuevo, Rafael Jimenez, Josvany Sanchez-Curbelo, Olga Lopez-Rodrigo, Maria Fernanda Peraza, Iris Pereira-Caetano, Patricia Isabel Marques, Filipa Carvalho, Alberto Barros, Lluis Bassas, Susana Seixas, Joao Goncalves, Sara Larriba, Alexandra Manuel Lopes, Francisco David Carmona, Rogelio Jesus Palomino-Morales
Summary: The study analyzed the impact of 6 single-nucleotide polymorphisms associated with NOA in the Iberian population, and found three variants linked to different manifestations of SpF. These variations may influence the development of spermatogenic failure by affecting gene expression and lincRNA deregulation.
Article
Biology
Katarzyna Jankowska, Natalia Suszczewicz, Michal Rabijewski, Piotr Dudek, Wojciech Zgliczynski, Radoslaw B. Maksym
Summary: Biochemical markers of spermatogenesis and fertility assessment are important in the management and prognosis of infertile males. Sperm count and inhibin B concentration are the best predictors of natural fertilization, and it is noteworthy that 81% of pregnancies were achieved without medically assisted reproduction.