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

Genes on the long arm of Y (Yq), particularly within interval 6, are believed to play a critical role in human spermatogenesis. Cytogenetically detectable deletions of this region are associated with azoospermia in men, but are relatively uncommon. It has been hypothesized that microdeletions of Yq may account for a significant proportion of men with infertility. The objective of this study was to validate a sequence-tagged site (STS)-mapping strategy for the detection of Yq microdeletions and to use this method to determine the proportion of men with idiopathic azoospermia or severe oligozoospermia who carry microdeletions in Yq. STS mapping of a sufficiently large sample of infertile men should also help further localize the putative gene(s) involved in the pathogenesis of male infertility. Genomic DNA was extracted from peripheral leukocytes of 16 normal fertile men, 7 normal fertile women, 60 infertile men (50 of whom had azoospermia and 10 of whom had severe oligozoospermia with no other recognizable cause of infertility), and 15 patients with the X-linked disorder, ichthyosis. PCR primers were synthesized for 26 STSs that span Yq interval 6. None of the 16 normal men of known fertility had microdeletions. Seven normal fertile women failed to amplify any of the 26 STSs, providing evidence of their Y specificity. No microdeletions were detected in any of the 15 patients with ichthyosis. Of the 60 infertile men typed with 26 STSs, 11 (18%; 10 azoospermic and 1 oligozoospermic) failed to amplify 1 or more STS. Interestingly, 4 of the 11 patients had microdeletions in a region that is outside the Yq region from which the DAZ (deleted in azoospermia gene region) gene was cloned. In an additional 3 patients, microdeletions were present both inside and outside the DAZ region. In 3 subjects, the microdeletions were verified by Southern analysis using labeled PCR products corresponding to the deleted STSs as probes. These data suggest a high prevalence (18%) of Yq microdeletions in men with idiopathic azoospermia/severe oligospermia. The physical locations of these microdeletions provide further support for the concept that a gene(s) on Yq deletion interval 6 plays an important role in spermatogenesis. The presence of deletions that do not overlap with the DAZ region suggests that genes other than the DAZ gene may also be implicated in the pathogenesis of some subsets of male infertility.
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PMID:Substantial prevalence of microdeletions of the Y-chromosome in infertile men with idiopathic azoospermia and oligozoospermia detected using a sequence-tagged site-based mapping strategy. 863 31

Some men with non-obstructive azoospermia harbour fully formed spermatozoa within their testicular tissue that can be used to achieve pregnancy via intracytoplasmic sperm injection (ICSI). Recently, Reijo et al. (1995) provided compelling evidence that the DAZ gene cluster is a strong candidate for one of the elusive azoospermia factors (AZF) located on the long arm of the Y chromosome. The DAZ gene cluster is deleted in 13% of azoospermic men and a small percentage of severely oligozoospermic men. Vertical transmission from father to son of AZF region deletions has also been described. Presumably these fathers were oligozoospermic. This led us to ask whether the azoospermic male with deletions of the AZF/DAZ region can also complete minimal spermatogenesis and whether any spermatozoa found could participate in fertilization, embryo development and pregnancy. Three out of six (50%) of the azoospermic men with AZF/DAZ deletions had spermatozoa identified within their harvested testicular tissue. When these spermatozoa were used for ICSI, fertilization occurred in 36% of injected oocytes. This compared favourably with testicular spermatozoa retrieved from non-obstructive azoospermic men without AZF/DAZ gene deletions. In one case, a twin conception resulted, which represents the first term pregnancy reported using spermatozoa from an AZF/DAZ deleted azoospermic male. Therefore it is necessary to take the possibility of transmission of infertility or sterility to our patients' offspring seriously when utilizing today's reproductive technologies, as spermatogenesis in men with AZF/DAZ deletions is by no means an exceptional occurrence.
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PMID:Azoospermic men with deletion of the DAZ gene cluster are capable of completing spermatogenesis: fertilization, normal embryonic development and pregnancy occur when retrieved testicular spermatozoa are used for intracytoplasmic sperm injection. 913 Jul 51

Microdeletions linked to deletion intervals 5 and 6 of the Y chromosome have been associated with male factor infertility. Members from at least two gene families lie in the region containing azoospermia factor (AZF), namely YRRM and DAZ. With the advent of intracytoplasmic sperm injection (ICSI), it is possible for men with severe male factor infertility to produce a child. The genetic consequences of such a procedure have been questioned. This report describes the first study of a population (32 couples) of infertile fathers and their sons born after ICSI. The objectives were firstly to determine the incidence and map location of Y chromosome microdeletions and to compare the frequencies with other population studies involving severe male factor infertility, and secondly to formulate a working hypothesis concerning developmental aetiology of Y chromosome microdeletions. The incidence of microdeletions in the ICSI population was shown to be 9.4% (within the range 9-18% reported for populations of severe male factor infertility patients). Microdeletions in two out of three affected father/son pairs mapped in the region between AZFb and AZFc and the third involved a large microdeletion in AZFb and AZFc. Of three affected father/son pairs, microdeletions were detected in the blood of one infertile propositus father and three babies. Assuming that the gonomes of the ICSI-derived babies are direct reflections of those of their fathers germ lines, it is possible that two of three infertile fathers were mosaic for intact Y and microdeleted Y chromosomes. In such cases, the developmental aetiology of the microdeletion may be due to a de-novo microdeletion arising as a post-zygotic mitotic error in the infertile propositus father, thus producing a mosaic individual who may or may not transmit the deletion to his ICSI-derived sons depending on the extent of primordial germ cell mosaicism. In one of three affected fathers, the microdeletion detected in his blood was also detected in his ICSI-derived son. In this case the de-novo event giving rise to the microdeletion may have occurred due to a post- (or pre-) meiotic error in the germ line of this father's normally fertile father (i.e. the ICSI-derived baby's grandfather).
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PMID:The incidence and possible relevance of Y-linked microdeletions in babies born after intracytoplasmic sperm injection and their infertile fathers. 923 38

Spermatogenesis is an elaborate process involving both cell division and differentiation, and cell-cell interactions. Defects in any of these processes can result in infertility, and in some cases these can be genetic in cause. Mapping experiments have defined at least three regions of the human Y chromosome that are required for normal spermatogenesis. Two of these contain the genes encoding the RNA binding proteins RBM and DAZ, suggesting that the control of RNA metabolism is likely to be an important control point for human spermatogenesis. A similar analysis in mice has shown that at least two regions of the mouse Y chromosome are essential for spermatogenesis. Both genetic and reverse genetic approaches have been used to identify mouse autosomal genes required for spermatogenesis. These studies have shown that genes in a number of different pathways are essential for normal spermatogenesis, and also provide putative models of human infertility.
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PMID:The molecular genetics of male infertility. 929 71

An overview is given about the current knowledge and research activities on the molecular analysis of interstitial deletions in the euchromatic part of the long arm of the human Y chromosome (Yq11). These mutations are associated with the male specific phenotype of azoospermia and severe oligozoospermia. The fact is stressed that only "de novo" microdeletions in Yq11 are of any diagnostic value in the infertility clinic because numerous polymorphic deletion events in Yq11 have also been reported. Three different "de novo" Yq11 microdeletions associated with male infertility are now found repeatedly (31 cases) in more than 700 patients. They strongly support the presence of at least three spermatogenesis loci in Yq11. They have been designated as AZFa, AZFb, and AZFc. Each of them should contain at least one Y gene functional in spermatogenesis and, if mutated, it should induce the same sterile phenotype as the corresponding AZF locus. These genes have not yet been found. However, some candidate genes exist: RBM for AZFb. DAZ and SPGY for AZFc. It is remarkable that all three encode testis specific RNA binding proteins with a similar sequence structure. Their structure and potential relationship is disussed.
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PMID:Human Y chromosome deletions in Yq11 and male fertility. 936 58

An apparently balanced reciprocal translocation 46,X,t(Y;6) (q11.23 approximately q12;p11.1) was observed in an infertile man with severe oligozooteratozoospermia. Different mitotic chromosome banding patterns were performed and fluorescence in situ hybridization indicated a breakpoint in the fluorescent Yq heterochromatin. Molecular genetic deletion experiments for the azoospermia factor region in distal Yq11 showed the retention of the DAZ gene and meiotic pairing configurations suggested that the man's infertility could be due to the pairing behaviour of the Y;6 translocation chromosome with the X chromosome visualised by synaptonemal complex analysis at the electron microscopy level. The morphological appearance of the normal chromosome 6 and the Y;6 translocated chromosome included in the compartment of the sex vesicle may allow an explanation of the degeneration of most spermatocytes after the pachytene stage.
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PMID:Y-autosome translocation and infertility: usefulness of molecular, cytogenetic and meiotic studies. 949 Mar 6

A constitutional de-novo deletion of the long arm of the Y chromosome was detected by standard cytogenetic analysis in a 38-year old male who, except for small testes and cryptozoospermia, was phenotypically normal. The deletion was further characterized by fluorescent in-situ hybridization (FISH) and digital image analysis using contigs of overlapping yeast artificial chromosome (YAC) clones, spanning almost the entire Y chromosome. These results showed that the deletion involved a large interstitial segment on the proximal long arm of the Y chromosome (Yq11.1-->Yq11.22) as well as a more distal portion of the Y chromosome, including the entire heterochromatic region (Yq11.23-->qter). The breakpoints as determined by the YAC probes were defined within the published Vergnaud intervals so that region 6B and 6C was mostly retained. However, the AZFc region harbouring the DAZ locus on distal subinterval 6F was lost in the deletion, making the absence of this region the most probable location for the patient's infertility. The data underline the usefulness of FISH as an alternative technique to conventional banding for the refined detection of chromosome Y deletions/rearrangements.
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PMID:Interstitial and terminal deletion of chromosome Y in a male individual with cryptozoospermia. 962 Aug 31

We evaluated whether deletions of the DAZ (deleted in azoospermia) gene, abnormal karyotypes or hypogonadotropic hypogonadism (HH) were demonstrable in infertile men who had undergone surgery in childhood for cryptorchidism with a simultaneous testicular biopsy that demonstrated no or almost no germ cells. In six men with infertility after surgery for cryptorchidism, the adult karyotype and analyses for the DAZ gene, serum follicle-stimulating hormone, luteinizing hormone, and testosterone were performed from a peripheral blood sample. Testicular volume was also measured. All patients exhibited a 46,XY karyotype. There were no deletions of the DAZ-gene, no HH and no testicular atrophy. The infertility was thus not proved to be congenital, and consequently, surgical treatment is indicated before the germ cells disappear from undescended testes. This appears to be before 15 months of age.
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PMID:Is infertility after surgery for cryptorchidism congenital or acquired? 988 Jun 85

To clarify whether cryptorchidism might be the expression of an intrinsic congenital testicular abnormality, we investigated the frequency of Y chromosome long arm (Yq) microdeletions in unilateral excryptorchid subjects manifesting an important bilateral testiculopathy. Microdeletion analysis of Yq was performed by polymerase chain reaction in the following subjects: 40 unilateral excryptorchid patients with azoospermia or severe oligozoospermia due to a bilateral severe testiculopathy (Sertoli cell-only syndrome or severe hypospermatogenesis); 20 unilateral excryptorchid men with moderate oligozoospermia and a normal testicular cytological picture in the contralateral testis; 110 patients affected by idiopathic severe primary testiculopathies; 20 patients affected by idiopathic moderate testiculopathy; and, as controls, 50 patients affected by known causes of testiculopathy and 100 fertile men. Eleven of 40 (27.5%) unilateral excryptorchid patients affected by bilateral testiculopathy and 28 of 110 (25.4%) patients affected by idiopathic severe primary testiculopathy showed Yq microdeletions, whereas no microdeletions were found in all the other subjects, nor in male relatives of patients with deletions. Microdeletions were located in different parts of Yq, including known regions involved in spermatogenesis (DAZ and RBM, AZFa, b, and c) and other loci still poorly defined. No difference in localization of deletions was evident between cryptorchid and idiopathic patients. Microdeletions in Yq may be responsible for severe bilateral testicular damage that could be phenotypically expressed by unilateral cryptorchidism, as well as by idiopathic infertility.
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PMID:Y chromosome microdeletions in cryptorchidism and idiopathic infertility. 1052 11

Deletions of the AZFc interval of the human Y chromosome are found in >5% of male patients with idiopathic infertility and are associated with a severely reduced sperm count. The most common deletion type is large (>1 Mb) and removes members of the Y-borne testis-specific gene families of BPY2, CDY1, DAZ, PRY, RBMY2 and TTY2, which are candidate AZF genes. Four exceptional individuals who have transmitted a large AZFc deletion naturally to their infertile sons have, however, been described. In three cases, transmission was to an only son, but in the fourth case a Y chromosome, shown to be deleted for all copies of DAZ, was transmitted from a father to his four infertile sons. Here we present a second family of this latter type and demonstrate that an AZFc-deleted Y chromosome lacking not only DAZ, but also BPY2 and CDY1, has been transmitted from a father to his three infertile sons. Polymerase chain reaction (PCR) and Southern blot analyses revealed no difference in the size of the AZFc deletion in the father and his sons. We propose that the father carries rare alleles of autosomal or X-linked loci which suppress the infertility that is frequently associated with the absence of AZFc.
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PMID:The human Y chromosome genes BPY2, CDY1 and DAZ are not essential for sustained fertility. 1095 50


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