scholarly journals A common 1.6 mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Pille Hallast ◽  
Laura Kibena ◽  
Margus Punab ◽  
Elena Arciero ◽  
Siiri Rootsi ◽  
...  
Keyword(s):  
Male Infertility ◽  
Genetic Factors ◽  
Gene Dosage ◽  
Severe Oligozoospermia ◽  
Azoospermia Factor ◽  
Reproductive Decision Making ◽  
High Penetrance ◽  
Carrier Identification ◽  
Factor C ◽  
Spermatogenic Failure

Male infertility is a prevalent condition, affecting 5–10% of men. So far, few genetic factors have been described as contributors to spermatogenic failure. Here, we report the first re-sequencing study of the Y-chromosomal Azoospermia Factor c (AZFc) region, combined with gene dosage analysis of the multicopy DAZ, BPY2, and CDYgenes and Y-haplogroup determination. In analysing 2324 Estonian men, we uncovered a novel structural variant as a high-penetrance risk factor for male infertility. The Y lineage R1a1-M458, reported at >20% frequency in several European populations, carries a fixed ~1.6 Mb r2/r3 inversion, destabilizing the AZFc region and predisposing to large recurrent microdeletions. Such complex rearrangements were significantly enriched among severe oligozoospermia cases. The carrier vs non-carrier risk for spermatogenic failure was increased 8.6-fold (p=6.0×10−4). This finding contributes to improved molecular diagnostics and clinical management of infertility. Carrier identification at young age will facilitate timely counselling and reproductive decision-making.

scholarly journals A common 1.6 Mb Y-chromosomal inversion predisposes to subsequent deletions and severe spermatogenic failure in humans

2020 ◽  
Author(s):  
Pille Hallast ◽  
Laura Kibena ◽  
Margus Punab ◽  
Elena Arciero ◽  
Siiri Rootsi ◽  
...  
Keyword(s):  
Male Infertility ◽  
Genetic Factors ◽  
Gene Dosage ◽  
Severe Oligozoospermia ◽  
Azoospermia Factor ◽  
Reproductive Decision ◽  
Reproductive Decision Making ◽  
Carrier Identification ◽  
Factor C ◽  
Spermatogenic Failure

AbstractMale infertility is a prevalent condition, concerning 5-10% of men. So far, only some recurrent genetic factors have been described as confident contributors to spermatogenic failure. Here, we report the first re-sequencing study of the Y-chromosomal Azoospermia Factor c (AZFc) region combined with gene dosage and Y-haplogroup determination. In analysing 2,324 Estonian men, we uncovered a novel structural variant as a high-penetrant risk factor to male infertility. The Y lineage R1a1-M458, reported at >20% frequency in several European populations, carries a fixed ∼1.6 Mb long r2/r3 inversion destabilizing the AZFc region and predisposing to recurrent microdeletions. Such complex rearrangements were significantly enriched among severe oligozoospermia cases. The carrier vs non-carrier risk to spermatogenic failure was increased 8.6-fold (p = 6.0 × 10−4). The finding contributes to improved molecular diagnostics and clinical management of infertility. Carrier identification in young age will facilitate timely counselling and reproductive decision-making.

scholarly journals Male Infertility Caused by a de Novo Partial Deletion of the DAZ Cluster on the Y Chromosome1

2000 ◽  
Vol 85 (11) ◽  
pp. 4069-4073
Author(s):  
Enrico Moro ◽  
Alberto Ferlin ◽  
Pauline Hsiao Yen ◽  
Paolo Guanciali Franchi ◽  
Giandomenico Palka ◽  
...  
Keyword(s):  
Male Infertility ◽  
De Novo ◽  
Point Mutations ◽  
De Novo Mutation ◽  
Specific Gene ◽  
Partial Deletion ◽  
Severe Oligozoospermia ◽  
First Case ◽  
Factor C ◽  
Spermatogenic Failure

Deletions in distal Yq interval 6 represent the cause of 10–15% of idiopathic severe male infertility and map to a region defined AZFc (azoospermia factor c). The testis-specific gene DAZ is considered a major AZFc candidate, and its deletion has been associated with a severe disruption in spermatogenesis. However, DAZ is actually a multicopy gene family consisting of seven clustered copies spanning about 1 megabase. Only deletions removing the entire DAZ gene cluster together with other genes have been reported in infertile males. Because no case of spermatogenic failure has been traced to intragenic deletions, point mutations, or even deletions not involving all the DAZ copies, the definitive proof for a requirement of DAZ for spermatogenesis is still debatable. Here we report the first case of a partial deletion of the DAZ cluster removing all but one of the copies. This deletion is present in a patient affected with severe oligozoospermia who had a testicular phenotype characterized by a great quantitative reduction of germ cells (severe hypospermatogenesis). The absence of this deletion in the fertile brother of the patient suggests that this de novo mutation indeed caused the spermatogenic failure.

Analysis of partial azoospermia factor c deletion andDAZcopy number in azoospermia and severe oligozoospermia

Andrologia ◽  
2016 ◽  
Vol 48 (9) ◽  
pp. 978-982 ◽  
Author(s):  
L. Alimardanian ◽  
K. Saliminejad ◽  
S. Razi ◽  
A. Ahani
Keyword(s):  
Severe Oligozoospermia ◽  
Azoospermia Factor ◽  
Factor C

GR/GR deletions within the azoospermia factor c region on the Y chromosome might not be associated with spermatogenic failure

2006 ◽  
Vol 85 (1) ◽  
pp. 229-231 ◽  
Author(s):  
Celia Ravel ◽  
Sandra Chantot-Bastaraud ◽  
Brahim El Houate ◽  
Jacqueline Mandelbaum ◽  
Jean-Pierre Siffroi ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Azoospermia Factor ◽  
Factor C ◽  
Spermatogenic Failure

The Association of Partial Azoospermia Factor C Deletions and Male Infertility in Northwestern China

2019 ◽  
Vol 84 (3) ◽  
pp. 144-150
Author(s):  
Chunlian Liu ◽  
Xinyan Zhao ◽  
Chunlan Mu ◽  
Hui Li ◽  
Jia Ma ◽  
...  
Keyword(s):  
Male Infertility ◽  
Northwestern China ◽  
Azoospermia Factor ◽  
Factor C

scholarly journals Molecular Characterization of Some Genetic Factors Controlling Spermatogenesis in Egyptian Patients with Male Infertility

2012 ◽  
Vol 3 (3) ◽  
pp. 69-77 ◽  
Author(s):  
Alaaeldin Gamal Fayez ◽  
Amr Saad El-Sayed ◽  
Mohamed Ali El-Desouky ◽  
Waheba Ahmed Zarouk ◽  
Alaa Khalil Kamel ◽  
...  
Keyword(s):  
Male Infertility ◽  
Y Chromosome ◽  
Copy Number ◽  
Genetic Factors ◽  
Gene Dosage ◽  
Copy Number Variations ◽  
Infertile Men ◽  
Egyptian Patients ◽  
Daz Gene

ABSTRACT Men with severe infertility suffer a high risk of Y chromosome deletion, hence screening for these cases is recommended prior to treatment with assisted reproduction. Our study aimed to investigate and detect the azoospermia factor (AZF) region deletion, rearrangement and deleted azoospermia (DAZ) gene copy number variations in Egyptian azoospermic infertile men. This was tested on 54 Egyptian nonobstructive azoospermic (NOA) infertile men, with age ranged from 21 to 45 years (mean: 31.4 ± 6.1 years), by STS ± multiplex PCR using a set of 14 sequence tagged sites (STSs) from three different regions of the Y chromosome: AZFa, AZFb, AZFc and sY587/DraI PCRRFLP assay to determine DAZ copy number variations. The results revealed a significant prevalence of AZFc subtypes deletion and reduced DAZ gene dosage in Egyptian azoospermic cases affecting Y chromosome deletions. To our knowledge, this study is the first one to investigate AZFc subtypes deletion and DAZ gene dosage in Egyptian infertile men. We concluded that DAZ genes deletion is a risk factor for spermatogenic damage. How to cite this article Fayez AG, El-Sayed AS, El-Desouky MA, Zarouk WA, Kamel AK, Fahmi IM, El-Ruby MO. Molecular Characterization of Some Genetic Factors Controlling Spermatogenesis in Egyptian Patients with Male Infertility. Int J Infertility Fetal Med 2012;3(3):69-77.

scholarly journals Y-chromosome haplogroups and susceptibility to azoospermia factor c microdeletion in an Italian population

2006 ◽  
Vol 44 (3) ◽  
pp. 205-208 ◽  
Author(s):  
B. Arredi ◽  
A. Ferlin ◽  
E. Speltra ◽  
C. Bedin ◽  
D. Zuccarello ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Italian Population ◽  
Azoospermia Factor ◽  
Factor C

scholarly journals Genetic Basis of Male Infertility

2013 ◽  
Vol 4 (1) ◽  
pp. 37-39 ◽  
Author(s):  
Mosammat Rashida Begum ◽  
Mariya Ehsan
Keyword(s):  
Genetic Testing ◽  
Male Infertility ◽  
Medical Treatment ◽  
Intracytoplasmic Sperm Injection ◽  
Chromosomal Abnormality ◽  
Genetic Disease ◽  
Genetic Basis ◽  
Common Cause ◽  
Near Future ◽  
Spermatogenic Failure

Infertility is a couple's problem. Almost 50% case males are responsible for infertility. Most common cause is oligospermia and azoospermia and approximately 5% to 15% of men with azoospermia and severe oligospermia may have a chromosomal abnormality. Men with significant spermatogenic compromise are the candidates of intracytoplasmic sperm injection (ICSI). Raised FSH level above 9 is an indication of spermatogenic compromise. So, medical treatment for these patients is waste of time and money. Early attempt of assisted reproduction is ideal to avoid the crisis of total spermatogenic failure in near future. But before going for ICSI genetic testing if possible and proper counseling about possibilities of transmission of genetic disease to offspring is necessary. DOI: http://dx.doi.org/10.3329/akmmcj.v4i1.13683 AKMMC J 2013: 4(1): 37-39  

scholarly journals Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel

2021 ◽  
Vol 11 ◽  
Author(s):  
Vincenza Precone ◽  
Rossella Cannarella ◽  
Stefano Paolacci ◽  
Gian Maria Busetto ◽  
Tommaso Beccari ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Male Infertility ◽  
Next Generation ◽  
Male Population ◽  
Pathogenic Variants ◽  
Custom Made ◽  
Number Of Genes ◽  
General Male Population ◽  
Generation Sequencing ◽  
Spermatogenic Failure

BackgroundInfertility affects about 7% of the general male population. The underlying cause of male infertility is undefined in about 50% of cases (idiopathic infertility). The number of genes involved in human spermatogenesis is over two thousand. Therefore, it is essential to analyze a large number of genes that may be involved in male infertility. This study aimed to test idiopathic male infertile patients negative for a validated panel of “diagnostic” genes, for a wide panel of genes that we have defined as “pre-diagnostic.”MethodsWe developed a next-generation sequencing (NGS) gene panel including 65 pre-diagnostic genes that were used in 12 patients who were negative to a diagnostic genetic test for male infertility disorders, including primary spermatogenic failure and central hypogonadism, consisting of 110 genes.ResultsAfter NGS sequencing, variants in pre-diagnostic genes were identified in 10/12 patients who were negative to a diagnostic test for primary spermatogenic failure (n = 9) or central hypogonadism (n = 1) due to mutations of single genes. Two pathogenic variants of DNAH5 and CFTR genes and three uncertain significance variants of DNAI1, DNAH11, and CCDC40 genes were found. Moreover, three variants with high impact were found in AMELY, CATSPER 2, and ADCY10 genes.ConclusionThis study suggests that searching for pre-diagnostic genes may be of relevance to find the cause of infertility in patients with apparently idiopathic primary spermatogenic failure due to mutations of single genes and central hypogonadism.

scholarly journals Testis-Specific SEPT12 Expression Affects SUN Protein Localization and is Involved in Mammalian Spermiogenesis

2019 ◽  
Vol 20 (5) ◽  
pp. 1163 ◽  
Author(s):  
Chung-Hsin Yeh ◽  
Ya-Yun Wang ◽  
Shi-Kae Wee ◽  
Mei-Feng Chen ◽  
Han-Sun Chiang ◽  
...  
Keyword(s):  
Male Infertility ◽  
Nuclear Membrane ◽  
Sperm Count ◽  
Protein Localization ◽  
Cancer Cell Line ◽  
Structural Defects ◽  
Preimplantation Embryos ◽  
Severe Oligozoospermia ◽  
Vitro Fertilization

Male infertility is observed in approximately 50% of all couples with infertility. Intracytoplasmic sperm injection (ICSI), a conventional artificial reproductive technique for treating male infertility, may fail because of a severe low sperm count, immotile sperm, immature sperm, and sperm with structural defects and DNA damage. Our previous studies have revealed that mutations in the septin (SEPT)-coding gene SEPT12 cause teratozoospermia and severe oligozoospermia. These spermatozoa exhibit morphological defects in the head and tail, premature chromosomal condensation, and nuclear damage. Sperm from Sept12 knockout mice also cause the developmental arrest of preimplantation embryos generated through in vitro fertilization and ICSI. Furthermore, we found that SEPT12 interacts with SPAG4, a spermatid nuclear membrane protein that is also named SUN4. Loss of the Spag4 allele in mice also disrupts the integration nuclear envelope and reveals sperm head defects. However, whether SEPT12 affects SPAG4 during mammalian spermiogenesis remains unclear. We thus conducted this study to explore this question. First, we found that SPAG4 and SEPT12 exhibited similar localizations in the postacrosomal region of elongating spermatids and at the neck of mature sperm through isolated murine male germ cells. Second, SEPT12 expression altered the nuclear membrane localization of SPAG4, as observed through confocal microscopy, in a human testicular cancer cell line. Third, SEPT12 expression also altered the localizations of nuclear membrane proteins: LAMINA/C in the cells. This effect was specifically due to the expression of SEPT12 and not that of SEPT1, SEPT6, SEPT7, or SEPT11. Based on these results, we suggest that SEPT12 is among the moderators of SPAG4/LAMIN complexes and is involved in the morphological formation of sperm during mammalian spermiogenesis.

Sign in / Sign up

Export Citation Format

Share Document