Chromosomal aneuploidies and associated rare genetic syndromes involved in male infertility

Mapping Intimacies ◽

10.31083/jomh.2021.016 ◽

2021 ◽

Keyword(s):

Male Infertility ◽

Chromosomal Abnormalities ◽

Genetic Disorders ◽

Molecular Genetic ◽

Unexplained Infertility ◽

Next Generation ◽

Genetic Syndromes ◽

Infertile Men ◽

Genetic Abnormalities ◽

Chromosomal Aneuploidies

Background and objectives: Recent investigations have reported more than 70 genetic syndromes involved in male infertility; however, the majority of these syndromes are extremely rare. We aimed to report the most common chromosomal abnormalities and associated rare genetic syndromes in the context of human male infertility. Materials and Methods: We performed a review of published articles considering the most common chromosomal aneuploidies and rare genetic syndromes associated with male infertility on PubMed, Web of Science, and Scopus. Results: Chromosomal abnormalities are frequently found in infertile men, with an incidence rate of 2-15%. The chromosomal aberrations include the sex and autosomal chromosome abnormalities, as well as numerical and structural defects in chromosomes. There are various rare genetic syndromes involved in male infertility that are caused by structural and numerical abnormalities in chromosomes. Klinefelter syndrome is the most common type of sex chromosome aneuploidy in infertile males. Besides, Y chromosome microdeletions, particularly in azoospermia factor regions, serve as the second most common genetic cause of impaired spermatogenetic in infertile men. These molecular genetic abnormalities not only can be inherited, but also they may transmit to the next generation through assisted reproductive techniques and result in the birth of boys with higher risk of congenital abnormalities and infertility. Despite the normal secondary male sexual characteristics, some patients are azoospermic or severe oligozoospermic men. Therefore, identiﬁcation of these molecular genetic factors and rare genetic disorders is essential in men with unexplained infertility. Discussion and conclusion: Since most of molecular genetic abnormalities can be transmitted to the next generation, identiﬁcation of these rare genetic disorders is crucial for men with unexplained infertility. It is also essential for clinicians and physicians of reproductive medicine and andrologists to initiate genetic evaluation, aneuploidy screening and counseling prior to any therapeutic procedures.

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Multicenter study of genetic abnormalities associated with severe oligospermia and non-obstructive azoospermia

Journal of International Medical Research ◽

10.1177/0300060517718771 ◽

2017 ◽

Vol 46 (1) ◽

pp. 107-114 ◽

Cited By ~ 13

Author(s):

Chong Xie ◽

Xiangfeng Chen ◽

Yulin Liu ◽

Zhengmu Wu ◽

Ping Ping

Keyword(s):

Genetic Testing ◽

Male Infertility ◽

Multicenter Study ◽

Chromosomal Abnormalities ◽

Eastern China ◽

Genetic Defects ◽

Obstructive Azoospermia ◽

Assisted Reproductive Technique ◽

Severe Oligozoospermia ◽

Genetic Abnormalities

Objective * Chong Xie, Xiangfeng Chen, and Yulin Liu contributed equally to this work. Genetic defects are identified in nearly 20% of infertile males. Determining the frequency and types of major genetic abnormalities in severe male infertility helps inform appropriate genetic counseling before assisted reproductive techniques. Methods Cytogenetic results of 912 patients with non-obstructive azoospermia (NOA) and severe oligozoospermia (SOS) in Eastern China were reviewed in this multicenter study from January 2011 to December 2015. Controls were 215 normozoospermic men with offspring. Results Among all patients, 22.6% (206/912) had genetic abnormalities, including 27.3% (146/534) of NOA patients and 15.9% (60/378) of SOS patients. Chromosomal abnormalities (all autosomal) were detected in only 1.9% (4 /215) of controls. In NOA patients, sex chromosomal abnormalities were identified in 25.8% (138/534), of which 8% (43/534) had a 47,XXY karyotype or its mosaic; higher than the SOS group prevalence (1.1%; 4/378). The incidence of Y chromosome microdeletions was lower in the SOS group (13.2%; 50/378) than in the NOA group (17.8%; 95/534). Conclusions The high prevalence of genetic abnormalities in our study indicates the importance of routine genetic testing in severe male infertility diagnosis. This may help determine the choice of assisted reproductive technique and allow specific pre-implantation genetic testing to minimize the risk of transmitting genetic defects.

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Surgical treatment of male infertility

10.1093/med/9780199659579.003.0097 ◽

2017 ◽

Author(s):

Gert R Dohle

Keyword(s):

Surgical Treatment ◽

Male Infertility ◽

Birth Defect ◽

Low Cost ◽

Unexplained Infertility ◽

Testis Cancer ◽

Obstructive Azoospermia ◽

Infertile Men ◽

Testis Volume ◽

Fair Chance

Surgical treatment of male infertility is indicated in men with obstructive azoospermia due to epididymal and vassal blockage, in infertile men with a varicocele and oligozoospermia, and to harvest spermatozoa for future intracytoplasmic sperm injection (ICSI). Testis biopsy may be performed in men with normal testis volume and normal gonadotrophins to confirm the diagnosis of obstructive azoospermia. Furthermore, testis biopsies are indicated in men with risk factors for testis cancer, such as infertility and ultrasonograhic abnormalities.Varicocele repair seems effective in case of an infertility duration of at least 2 years, oligozoospermia, and otherwise unexplained infertility in a couple. The advantages of surgery in these couples are a fair chance of spontaneous pregnancies at relative low cost and with less obstetric problems and birth defect compared to pregnancies from IVF procedures.

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Male infertility in China: laboratory finding for AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China

Journal of Assisted Reproduction and Genetics ◽

10.1007/s10815-010-9420-9 ◽

2010 ◽

Vol 27 (7) ◽

pp. 391-396 ◽

Cited By ~ 25

Author(s):

Rui-Xue Wang ◽

Chao Fu ◽

Ya-Ping Yang ◽

Rong-Rong Han ◽

Yuan Dong ◽

...

Keyword(s):

Male Infertility ◽

Chromosomal Abnormalities ◽

Laboratory Finding ◽

Northeastern China ◽

Infertile Men

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Methylation of the SNRPN gene in infertile men without mutations in common candidate genes for reduced fertility

Andrology and Genital Surgery ◽

10.17650/1726-9784-2021-22-1-52-61 ◽

2021 ◽

Vol 22 (1) ◽

pp. 52-61

Author(s):

D. S. Mikhaylenko ◽

О. A. Simonova ◽

I. El Akel ◽

I. Yu. Sobol ◽

Т. A. Edoyan ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Male Infertility ◽

Molecular Genetic ◽

Significant Proportion ◽

Point Mutations ◽

Aberrant Methylation ◽

Chain Reaction ◽

Infertile Men ◽

Monogenic Diseases ◽

Polymerase Chain

Introduction. Male infertility is a common problem in andrology and occurs in 45 % of infertile couples. Some cases of male infertility caused by genetic reasons: point mutations at some monogenic diseases, AZF deletions or a CFTR mutation compounds; reduced fertility is also associated with polymorphic variants of the genes AR and GSTT1/GSTM1. At the same time, increasing amount of data are being published about the role of epigenetic mechanisms (aberrant methylation and imprinting alterations) in defective spermatogenesis.Materials and methods. We have studied 49 sperm samples obtained from unrelated infertile men using polymerase chain reaction, fragment analysis, and sequencing.Results. Five patients were excluded from the initial cohort: one with a repeat length of 29 (CAG) in the first exon of the AR, three with null genotypes in the GSTT1 and GSTM1, and one with the delF508/5T heterozygous compound in the CFTR. Thereafter, methylation of the imprinted gene SNRPN was determined using methyl-specific polymerase chain reaction and bisulfite sequencing. Aberrant SNRPN methylation was detected in 11.4 % of male infertility samples. In total, molecular genetic and epigenetic alterations were determined in 20 % of patients.Conclusions. Obtained data demonstrate a significant proportion of (epi)genetic disorders in a heterogeneous cohort of men with reduced fertility.

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Update on genetic screening and treatment for infertile men with genetic disorders in the era of assisted reproductive technology

Clinical and Experimental Reproductive Medicine ◽

10.5653/cerm.2021.04476 ◽

2021 ◽

Author(s):

Seung Ryeol Lee ◽

Tae Ho Lee ◽

Seung-Hun Song ◽

Dong Suk Kim ◽

Kyung Hwa Choi ◽

...

Keyword(s):

Male Infertility ◽

Genetic Basis ◽

Genetic Disorders ◽

Genetic Diseases ◽

Testicular Sperm Extraction ◽

Vitro Fertilization ◽

Infertile Men ◽

Generation Sequencing

A genetic etiology of male infertility is identified in fewer than 25% of infertile men, while 30% of infertile men lack a clear etiology, resulting in a diagnosis of idiopathic male infertility. Advances in reproductive genetics have provided insights into the mechanisms of male infertility, and a characterization of the genetic basis of male infertility may have broad implications for understanding the causes of infertility and determining the prognosis, optimal treatment, and management of couples. In a substantial proportion of patients with azoospermia, known genetic factors contribute to male infertility. Additionally, the number of identified genetic anomalies in other etiologies of male infertility is growing through advances in whole-genome amplification and next-generation sequencing. In this review, we present an up-to-date overview of the indications for appropriate genetic tests, summarize the characteristics of chromosomal and genetic diseases, and discuss the treatment of couples with genetic infertility by microdissection-testicular sperm extraction, personalized hormone therapy, and in vitro fertilization with pre-implantation genetic testing.

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Y Chromosome deletions and male infertility

Reproductive Medicine Review ◽

10.1017/s0962279900001393 ◽

1997 ◽

Vol 6 (1) ◽

pp. 37-53 ◽

Cited By ~ 4

Author(s):

D M de Kretser ◽

C Mallidis ◽

K Ma ◽

S Bhasin

Keyword(s):

Y Chromosome ◽

Chromosomal Abnormalities ◽

Genetic Disorders ◽

Male Partner ◽

Testicular Feminization ◽

Sperm Production ◽

The Past ◽

Infertile Men ◽

Gene Defects ◽

Chromosome Deletions

Approximately one in ten couples experience infertility, and in about 40% of these infertile unions there are abnormalities in the fertility of the male partner. The clinical management of these infertile men is less than satisfactory because in 40% of such patients the cause of the abnormalities of sperm production and quality is unknown. The possibility that genetic disorders may account for a proportion of these disturbances of sperm production has been raised. It is well recognized that chromosomal abnormalities such as Klinefelter's syndrome cause azoospermia and that gene defects are the basis of testicular feminization, Kallman's syndrome and Reifenstein's syndrome. With the explosion in our knowledge of the human genome, the possibility exists that other genetic disorders may form the basis of other sperma-togenic abnormalities. The past decade has witnessed the accumulation of evidence linking abnormalities of the Y chromosome with disturbances in sperm production and these observations form the basis of this review.

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The influence of Robertsonian translocations on semen parameters

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.03.87-88 ◽

2020 ◽

pp. 87-88

Author(s):

М.В. Андреева ◽

М.И. Штаут ◽

Т.М. Сорокина ◽

Л.Ф. Курило ◽

В.Б. Черных

Keyword(s):

Male Infertility ◽

Semen Parameters ◽

Meiotic Arrest ◽

Robertsonian Translocations ◽

Prophase I ◽

Infertile Men ◽

Fertility Problems ◽

Spermatogenesis Impairment

Обследованы 19 мужчин с нарушением фертильности, носителей транслокаций rob(13;14) и rob(13;15). Показано, что нарушение репродуктивной функции обусловлено блоком сперматогенеза в профазе I мейоза, приводящего к азооспермии или олигоастенотератозооспермии и мужскому бесплодию. We examined 19 infertile men, carriers of translocations rob (13;14) and rob (13;15). We assume that fertility problems are resulted from spermatogenesis impairment because of meiotic arrest at prophase I stages, that leads to azoospermia or oligoastenoteratozoospermia and male infertility.

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Idiopathic Infertility as a Feature of Genome Instability

Life ◽

10.3390/life11070628 ◽

2021 ◽

Vol 11 (7) ◽

pp. 628

Author(s):

Agrita Puzuka ◽

Baiba Alksere ◽

Linda Gailite ◽

Juris Erenpreiss

Keyword(s):

Life Expectancy ◽

Male Infertility ◽

Genome Instability ◽

Repair System ◽

Environmental Aspects ◽

Strand Breaks ◽

Testicular Dysfunction ◽

Infertile Men ◽

Dna Strand ◽

Dynamic Mutations

Genome instability may play a role in severe cases of male infertility, with disrupted spermatogenesis being just one manifestation of decreased general health and increased morbidity. Here, we review the data on the association of male infertility with genetic, epigenetic, and environmental alterations, the causes and consequences, and the methods for assessment of genome instability. Male infertility research has provided evidence that spermatogenic defects are often not limited to testicular dysfunction. An increased incidence of urogenital disorders and several types of cancer, as well as overall reduced health (manifested by decreased life expectancy and increased morbidity) have been reported in infertile men. The pathophysiological link between decreased life expectancy and male infertility supports the notion of male infertility being a systemic rather than an isolated condition. It is driven by the accumulation of DNA strand breaks and premature cellular senescence. We have presented extensive data supporting the notion that genome instability can lead to severe male infertility termed “idiopathic oligo-astheno-teratozoospermia.” We have detailed that genome instability in men with oligo-astheno-teratozoospermia (OAT) might depend on several genetic and epigenetic factors such as chromosomal heterogeneity, aneuploidy, micronucleation, dynamic mutations, RT, PIWI/piRNA regulatory pathway, pathogenic allelic variants in repair system genes, DNA methylation, environmental aspects, and lifestyle factors.

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