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Query: UMLS:C0021359 (infertility)
 26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genes on Y-chromosome are involved in the regulation of spermatogenesis. Y-chromosome microdeletions were identified among infertile patients in a frequency of 7.5-15% on the long arm of the chromosome. These microdeletions were clustered in 3 main regions named AZFa, AZFb, and AZFc. Reanalyzing the histological findings in men with well-defined varying extent of Y-chromosome microdeletions improved our understanding of the prospect of finding testicular spermatozoa. The chances of finding spermatozoa were almost nil in men with microdeletions that include the complete AZFa region or AZFb region or at least two AZF regions. Large microdeletions that include the Yq tip were suggested to cause chromosomal instability and were shown to be prone to Y chromosome loss. In addition, a decrease of sperm count over time in men with AZFc deletions has been reported and the option of spermatozoa cryo-preservation need to be taken in consideration. Analysis of the Y-chromosome microdeletion was found to be of prognostic value in cases of infertility both in terms of clinical management as well as for understanding the etiology of the spermatogenesis impairment.
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PMID:[The prognostic value of the site and extent of Y chromosome microdeletions on spermatogenesis]. 1190 91

The incidence of Y/autosome translocations is low. Whereas involvement of non-acrocentric chromosomes often leads to infertility, cases related with acrocentric chromosomes are usually familial with no or minimal effect on fertility. A de novo (Yp/13p) translocation was found in a 32-year-old male referred for severe oligozoospermia. Conventional cytogenetic procedures (GTG, CBG and NOR banding) and molecular cytogenetic techniques (Fluorescence In Situ Hybridization, FISH) were performed on high-resolution chromosomes obtained after peripheral blood lymphocyte culture as also on interphase nuclei of spermatogenic cells from semen samples. Screening of AZF microdeletions in the Yq11.2 region known to be involved with spermatogenesis defects was also performed. GTG banding showed a (Yp/13p) translocation in all scored metaphases. CBG and NOR staining of the derivative chromosome revealed the maintenance of Yq heterochromatin and of the 13p NOR region. FISH with centromeric Y and 13/21 probes, SRY specific probe and X/Y (p and q arms) sub-telomeric probes gave the expected number/location of fluorescent signals. Hybridisation with a pan-telomeric repeat (TTAGGG) probe showed an absence of the telomeric sequences at the fusion point of the rearranged chromosome. FISH analysis with probes to chromosomes X, Y, 13 and 18 showed an abnormal segregation of the translocated chromosome during meiosis I, which explains that only 13.6% of the secondary spermatocytes were normal. Most of these became arrested, as after meiosis II the large majority of the round spermatids were normal (70%), as were in consequence most of the sperm (85.1%). Multiplex-PCR confirmed the intactness of the SRY region and showed absence of AZF microdeletions. We report a novel de novo (Yp;13p) translocation characterised by loss of the 13p and Yp telomeres. Meiotic studies using FISH demonstrated meiosis I chromosome unpairing and mal segregation that justifies the severe oligozoospermia. Although most sperm have a normal chromosomal constitution, preimplantation genetic diagnosis should be considered an option for this patient.
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PMID:Unique (Y;13) translocation in a male with oligozoospermia: cytogenetic and molecular studies. 1211 41

About 30% of couple infertilities are of male origin, some of them caused by genetic abnormalities of the Y chromosome. Deletions in AZF region can cause severe spermatogenic defects ranging from non-obstructive azoospermia to oligospermia. The intracytoplasmatic sperm injection technique (ICSI) is rapidly becoming a versatile procedure for human assisted reproduction in case of male infertility. The use of ICSI allows Y chromosome defects to be passed from father. The goal of our study is to evaluate the frequency of microdeletions in the long arm of Y chromosome, within the AZF regions, in these cases of infertilities, using molecular genetics techniques. Thirty infertile men with azoospermia or oligozoospermia, determined by spermogram, were studied after exclusion of patients with endocrine or obstructive causes of infertility. Peripheral blood DNA was extracted from each patient, then amplified by multiplex PCR with STS genomic markers from the Y chromosome AZF zones. Each case was checked by multiplex PCR through coamplification with the SRY marker. Three men with microdeletions of the long arm of the Y chromosome were diagnosed among the 30 patients, corresponding to a proportion of 10%. The relatively high proportion of microdeletions found in our population suggest the need for strict patient selection to avoid unnecessary screening for long arm Y chromosome microdeletions. The molecular diagnostics was performed according to the current European Academy of Andrology laboratory guidelines for molecular diagnosis of Y chromosomal microdeletions.
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PMID:Screening for microdeletions in human Y chromosome--AZF candidate genes and male infertility. 1276 60

Human spermatogenesis failures appear frequently as idiopathic and may be due to genetic causes. Mutations of genes involved in the hypothalamic/pituitary control of spermatogenesis have been described and account for several types of hypogonadotropic hypogonadism. Chromosomal abnormalities found in infertile patients are either gonosomal aneuploidies or structural anomalies which interfere with the normal chromosome behaviour at meiosis and lead to germ cell breakdown. Microdeletions of the Y chromosome are often undetectable at karyotype and are responsible for the loss of genes which compose the AZF factor. The increase in the number of mouse models of infertility will allow the description of many human genes involved in the spermatogenesis process provided that a detailed analysis of their genotype-phenotype relationships is performed.
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PMID:[Genetic origin of spermatogenesis impairments: clinical aspects and relationships with mouse models of infertility]. 1286 88

Testicular germ cell cancer is aetiologically linked to genital malformations and male infertility and is most probably caused by a disruption of embryonic programming and gonadal development during fetal life. In some cases, germ cell neoplasia is associated with a relative reduction of Y chromosomal material (e.g. 45,X/46,XY) or other abnormalities of the Y chromosome. The euchromatic long arm of the human Y chromosome (Yq11) contains three azoospermia factors (AZFa, AZFb, AZFc) functionally important in human spermatogenesis. Microdeletions encompassing one of these three AZF loci result in the deletion of multiple genes normally expressed in testis tissue and are associated with spermatogenic failure. The aim of our study was to investigate whether AZF microdeletions, in addition to causing infertility, predispose also to germ cell neoplasia, since subjects with poor spermatogenesis have an increased risk of testicular cancer. We screened for putative deletions of AZF loci on the Y chromosome in DNA isolated from white blood cells of 160 Danish patients with testicular germ cell neoplasia. Interestingly, although AZF microdeletions are found frequently in patients with idiopathic infertility, in all cases studied of testicular germ cell cancer the Yq region was found to be intact. We conclude that the molecular aetiology of testicular germ cell neoplasia of the young adult type most likely does not involve the same pathways as male infertility caused by AZF deletions. Malignant transformation of germ cells is thus caused by the dysfunction of some other genes that still need to be identified.
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PMID:No AZF deletion in 160 patients with testicular germ cell neoplasia. 1290 May 10

Chromosomal and Y-chromosomal microdeletion analysis has been done in cases of idiopathic infertility with the objective of evaluating the frequency of chromosomal and molecular anomaly as the causal factor of infertility. Barring a few cases of Klinefelter syndrome (XXY or XY/XXY mosaics), no chromosomal anomaly was encountered. Y-microdeletion was analysed by PCR-screening of STSs from different regions of the AZF (AZFa, AZFb, AZFc) on the long arm of the Y, as well as by using DNA probes of the genes RBM, DAZ (Yq), DAZLA (an autosomal homologue of DAZ) and SRY (Yp; sex determining gene). Out of 177 cases examined, 9 (azoospermia - 8 and oligoasthenospermia - 1) showed partial deletion of AZF. The size of deletion varied among patients but AZFc was either totally or partially removed in all of them. In contrast, no deletion was detected in AZFa. Testis biopsy done on a limited number of cases (50) showed diverse stages of spermatogenic arrest with no specific correlation with the genotype. The frequency of Y-chromosome microdeletion in our samples (approximately 5%) is much lower than the frequency (approximately 10%) reported globally and the two previous reports from India. We contend that the frequency may be affected by population structures in different geographical regions.
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PMID:Idiopathic cases of male infertility from a region in India show low incidence of Y-chromosome microdeletion. 1451 64

The human Y chromosome contains over 60 million nucleotides, but least number of genes compared to any other chromosome and acts as a genetic determinant of the male characteristic features. The male specific region, MSY, comprising 95% of the Y chromosome represents a mosaic of heterochromatic and three classes of euchromatic (X-transposed, X-degenerate and ampliconic) sequences. Thus far, 156 transcription units, 78 protein-coding genes and 27 distinct proteins of the Y chromosome have been identified. The MSY euchromatic sequences show frequent gene conversion. Of the eight massive palindromes identified on the human Y chromosome, six harbor vital testis specific genes. The human male infertility has been attributed to mutations in the genes on Y chromosome and autosomes and failures of several physical and physiological attributes including paracrine controls. In addition, deletion of any one or all the three azoospermia (AZFa, AZFb or AZFc) factor(s) and some still unidentified regulatory elements located elsewhere in the genome result in infertility. Characterization of palindromic complexes on the long arm of Y chromosome encompassing AZFb and AZFc regions and identification of HERV15 class of endogenous retroviruses close to AZFa region have facilitated our understanding on the organization of azoospermia factors. Considerable overlap of the AZFb and AZFc regions encompassing a number of genes and transcripts has been shown to exist. However, barring details on AZF, information on the exact number of genes or the types of mutations prevalent in the infertile male is not available. Similarly, roles of sizable body of repetitive DNA present in close association with transcribing sequences on the Y chromosome are yet not clear. In a clinical setting with known cases of infertility, systematic search for loss or gain of these repeat elements would help understand their biological role(s). We present a brief overview on the genetic complexity of the human Y chromosome in the context of human male infertility.
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PMID:Genomics of the human Y-chromosome. 1. Association with male infertility. 1463 89

Genetic lesions causing human male infertility are manifold. Besides gross chromosomal aneuploidies and rearrangements, microdeletions and single gene defects can interfere with male fertility. Male fertility is not only dependent on genes controlling the male germ line but also on genes of the networks functional for male gonad development and male somatic development, respectively. It is popular to unravel these netweorks with mouse gene knock-out mutants displaying reproductive defects. However, substantial arguments can be given for more functional studies directly on the human genes, because multiple reproductive proteins evolve quickly most likely for adopting to the specific needs of the species class. Prominent examples are mutations of the FSHR gene causing different pathologies in mouse and human and the DAZ gene family not found in the mouse genome but in the human genome with an essential male fertility function. Therefore this review is focussed on a comprehensive overview of human genes known with mutations causing male infertility (AR; AZF gene families; CFTR, DM-1, DNAH gene family, FGFR1, FSHR, INSL3, KAL-1, LGR8- GREAT, LHR, POLG). Then some human genes are described well recognised as functional in spermatogenesis and male fertility although gene specific mutations causing infertility were not yet identified (CREM, CDY1, DAZL1, PHGPx, PRM-1, PRM-2). They are designated as "spermatogenesis phase marker" or "male fertility index" genes, because they are useful tools for diagnosing the patient's spermatogenesis disruption phase and for predicting the presence and quality of his mature sperms. Current therapeutic protocols for human male infertility do usually not cure the specific gene defect but try to bypass it using Artificial Reproductive Technology (ART). Putative imprinting defects in the early embryo probably associated with the used ART protocol and an increase of chromosome abnormalities in the ART offspring now strongly asks for a significant improvement of this outcome requesting urgently more basic research on the genes functioning in the human male germ line and during early human embryogenesis.
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PMID:Molecular genetics of human male infertility: from genes to new therapeutic perspectives. 1496 34

The aetiology of compromised spermatogenesis is often genetic in nature. There are only a few reports of father/son cohorts that have been evaluated to assess heritability of mutations associated with male factor infertility and the psychological well-being of the children. In the present study, multiple tissues were sampled from consenting male patients and their sons derived from intracytoplasmic sperm injection (ICSI) and underwent chromosomal and genetic analyses. Paediatric and psychological examinations were also conducted. In 87 men and 47 boys, 22 sequence tagged sites (STS) were analysed by multiplex PCR and deletion breakpoints were defined with additional loci. In one patient, the breakpoints map to the highly unstable palindrome-rich region within AZFb and proximal AZFc was investigated. A total of 86 blood, 26 semen, and 73 cheek cells samples were collected from adults, and 36 blood samples and 44 cheek cell specimens were obtained from the boys. Though all of the fathers had normal karyotypes, the incidence of chromosomal abnormalities in the somatic cells of male progeny was 8.3% (3/36). The incidence of germ line aneuploidy in these men was 0.5-2.8%. A CF mutation (Delta508) was detected in one of 87 men (1.2%) and microdeletions in Yq AZF were detected in 3.4% of 87 adults and in 2.1% of their sons (n = 47). In conclusion, screening for Y chromosome microdeletions provides crucial information in the counselling of couples seeking infertility treatment. Moreover, DNA extraction and Y deletion assessments of cheek cells provide a non-invasive approach. Inheritance of Yq deletions appears not to affect the psychological and physical development of children derived from ICSI.
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PMID:Y chromosome assessment and its implications for the development of ICSI children. 1503 96

Seventy-six percent of testicular cancers of origin in Finns have been reported to exhibit AZF deletions. We analyze here 40 testicular tumor cases from Norway and Argentina and we found that AZF deletions occur also in non-Finnish cases but at significantly lower frequency (25%) than in Finland testicular tumor cases. This frequency difference can be attributed to the condition of genetic isolate of the Finnish population and the subsequent prevalence in this ethnic group of genetic factors involved in the origin of AZF deletions associated with malignancies. The finding of a correlation between AZF deletions and a given Y haplogroup would indicate the existence of Y lineages carrying AZF deletion-enhancing gene or genes. This possibility was explored using a set of Y-DNA-markers allowing the identification of Y lineages occurring at high frequency in Finns. We characterized the Y haplogroups in 32 normal Finn males (control group) and 17 cases of testicular cancer in Finns with and without AZF deletions. We found no association between Y lineages and AZF microdeletions, nor between AZF microdeletions and a Y microdeletion (DYS7C) exhibiting high prevalence (>50%) in Finns. The lack of correlation between AZF deletions and Y haplogroups indicates that the origin of these deletions is independent from the Y chromosome genetic background. No AZF deletions were found in familial cases of testicular tumors; hence, hereditary factors inducing the appearance of testicular malignancies in certain genealogies apparently do not increase the susceptibility to AZF deficiencies. AZF deletions are de novo events occurring in prezygotic or in post-zygotic stages. We propose that most AZF deletions associated with testicular tumors are due to post-zygotic Y microdeletions, while most cases of deletions associated with infertility are due to deletions occurring in the germ cell line of proband fathers.
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PMID:Ethnic variation in the prevalence of AZF deletions in testicular cancer. 1545 Apr 3


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