102 results on '"spermatogenic failure"'
Search Results
2. P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure
- Author
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Lardone, M. C., Castillo, P., Valdevenito, R., Ebensperger, M., Ronco, A. M., Pommer, R., Piottante, A., and Castro, A.
- Published
- 2010
- Full Text
- View/download PDF
3. A nation-based population screening for azoospermia factor deletions in Greek-Cypriot patients with severe spermatogenic failure and normal fertile controls, using a specific study and experimental design
- Author
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Ioulianos, A, Sismani, C, Fourouclas, N, Patroclou, T, Sergiou, C, and Patsalis, P. C
- Published
- 2002
4. DAZL polymorphisms and susceptibility to spermatogenic failure: an example of remarkable ethnic differences
- Author
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Becherini, L., Guarducci, E., DeglʼInnocenti, S., Rotondi, M., Forti, G., and Krausz, C.
- Published
- 2004
5. A to G transitions at 260, 386 and 437 in DAZL gene are not associated with spermatogenic failure in Indian population
- Author
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Kumarasamy Thangaraj, S.R. Deepa, P. Reddy, Kadupu Pavani, Alla G. Reddy, Nalini J. Gupta, Baidyanath Chakravarty, and Lalji Singh
- Subjects
Infertility ,Male ,Guanine ,Urology ,Endocrinology, Diabetes and Metabolism ,Population ,India ,Single-nucleotide polymorphism ,Biology ,medicine.disease_cause ,Male infertility ,Andrology ,DAZL ,medicine ,Humans ,Point Mutation ,education ,Azoospermia ,Genetics ,Mutation ,education.field_of_study ,Point mutation ,Adenine ,RNA-Binding Proteins ,Oligospermia ,medicine.disease ,Reproductive Medicine - Abstract
Summary The autosomal DAZL (Deleted-in-Azoospermic-Like) gene, mapped to the short arm of the human chromosome 3, is the precursor for the Y-chromosomal DAZ cluster, which encodes for putative RNA-binding proteins. Mutations in the DAZL have been reported to be associated with spermatogenic failure in Taiwanese population but not in Caucasians. As there was no study on Indian populations, we have analysed the entire coding sequences of exons 2 and 3 of DAZL in a total of 1010 men from Indian subcontinent, including 660 infertile men with 598 non-obstructive azoospermia, 62 severe oligozoospermia and 350 normozoospermic fertile control men, to investigate whether mutation(s) in the DAZL is associated with male infertility. Interestingly, none of our samples (1010) showed A386G (T54A) mutation, which was found to be associated with spermatogenic failure in Taiwanese population. In contrast, A260G (T12A) mutation was observed in both infertile and normozoospermic fertile control men, without any significant association with infertile groups (χ2 = 0.342; p = 0.556). Similarly, we have found a novel A437G (I71V) mutation, which is also present in both infertile and normozoospermic fertile control men without any significant difference (χ2 = 0.476; p = 0.490). Our study clearly demonstrates the complete absence of the A386G (T54A) mutation in Indian subcontinent and the other two mutations – A260G (T12A) and A437G (I71V) – observed are polymorpic. Therefore, we conclude that these mutations in the DAZL gene are not associated with male infertility in Indian subcontinent.
- Published
- 2006
6. A nation-based population screening for azoospermia factor deletions in Greek-Cypriot patients with severe spermatogenic failure and normal fertile controls, using a specific study and experimental design
- Author
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Philippos C. Patsalis, A. Ioulianos, T. Patroclou, Carolina Sismani, N. Fourouclas, and C. Sergiou
- Subjects
Male ,medicine.medical_specialty ,Y chromosome microdeletion ,Urology ,Endocrinology, Diabetes and Metabolism ,Population ,Obstructive azoospermia ,Ethnic origin ,Biology ,Internal medicine ,Y Chromosome ,medicine ,Humans ,education ,Spermatogenesis ,Sequence Tagged Sites ,Azoospermia ,Gynecology ,education.field_of_study ,Azoospermia factor ,Greece ,Seminal Plasma Proteins ,Oligospermia ,medicine.disease ,Reproductive Medicine ,Genetic Loci ,Research Design ,Case-Control Studies ,Cyprus ,Population study ,Chromosome Deletion ,Gene Deletion - Abstract
Y chromosome microdeletions in the azoospermia factor (AZF) locus have been associated with spermatogenic failure. The frequency of AZF deletions is estimated to be about 10-18% in subgroups of idiopathic azoospermia and severe oligospermia, whereas the deletion frequency is estimated to be about 1.5-10.6% in the general population. Patient selection criteria as well as experimental and study design are the major factors that influence the deletion frequency. We designed a nation-based population screening with a well-defined study and experimental criteria to answer, first, what is the deletion frequency in a study population of high risk for Y deletion in the Greek-Cypriot origin and second, if there are any differences in the deletion frequency in the investigated specific subgroup of patients from different geographic/ethnic origin. Eighty Greek-Cypriot patients who met the selection criteria were included in this study as well as 50 fertile control males. The sample size is quite large when compared with the size of the population. All samples were collected from all districts of the island of Cyprus as the population is of the same religious, geographic and ethnic origin. All patients and controls had detailed clinical information and at least two semen-analysis reports based on World Health Organization standards. Samples with abnormal karyotypes, obstructive azoospermia or oligospermia with >2 × 10 6 /mL were excluded from this study. The experimental design required a referral team and laboratory to undertake the responsibility to collect all the samples, all clinical and laboratory information, isolate DNA and carry out all tests, data analysis and interpretation. In our study, Y chromosome microdeletions have been found in patients with spermatogenic failure. Under the specific patient selection criteria and experimental design, the overall frequency is 5%, while among azoospermic patients it is 12.5%. In the subgroups of patients with idiopathic cause it is 5.9% and in idiopathic azoospermia it is 14.3%. No variation in the overall deletion frequency or the specific subgroups deletion frequency were found, as compared with frequencies found in patients from different geographic/ethnic origin.
- Published
- 2002
7. DAZL polymorphisms and susceptibility to spermatogenic failure: an example of remarkable ethnic differences
- Author
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L. Becherini, Csilla Krausz, E. Guarducci, Gianni Forti, Selene Degl’Innocenti, and Mario Rotondi
- Subjects
Genetics ,Azoospermia ,Male ,DAZL ,genetics ,male infertility ,polymorphism ,spermatogenesis ,Polymorphism, Genetic ,Urology ,Endocrinology, Diabetes and Metabolism ,RNA-Binding Proteins ,Single-nucleotide polymorphism ,Biology ,medicine.disease ,Phenotype ,Male infertility ,Reproductive Medicine ,Multigene Family ,Gene cluster ,medicine ,Ethnicity ,Coding region ,Humans ,Gene - Abstract
Polymorphisms in genes involved in spermatogenesis are considered potential risk factors for male infertility. Recently a polymorphism in the deleted in azoospermia-like (DAZL) gene (T54A) was reported as susceptibility factor to oligo/azoospermia in the Chinese population. DAZL is an autosomal homologue of the Y chromosomal DAZ (deleted in azoospermia) gene cluster and both are considered master regulators of spermatogenesis. The aim of the present study was to screen (i) for mutations of the entire coding sequence of the DAZL gene in patients lacking of the DAZ gene cluster, in order to evaluate if DAZL polymorphisms may influence the AZFc deletion phenotype; (ii) for the two previously described (and eventually newly identified) single nucleotide polymorphisms (SNPs) in a large group of infertile and normospermic men of Italian origin. We failed to detect new mutations. We confirmed previous results showing no evidence for a functional role of the T12A mutation. Surprisingly, the T54A polymorphism, which was present in 7.4% of the Chinese patients was absent in our Caucasian population. This remarkable difference represent an example of how ethnic background is important also for polymorphisms involved in spermatogenesis and contributes to better select clinically relevant tests, specifically based on the ethnic origin of the infertile patients.
- Published
- 2004
8. P450-aromatase activity and expression in human testicular tissues with severe spermatogenic failure
- Author
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Lardone, M. C., primary, Castillo, P., additional, Valdevenito, R., additional, Ebensperger, M., additional, Ronco, A. M., additional, Pommer, R., additional, Piottante, A., additional, and Castro, A., additional
- Published
- 2009
- Full Text
- View/download PDF
9. An evolutionary perspective on Y-chromosomal variation and male infertility
- Author
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Chris Tyler-Smith
- Subjects
Male ,Urology ,Endocrinology, Diabetes and Metabolism ,Single-nucleotide polymorphism ,Biology ,Population stratification ,Y chromosome ,Genome ,Male infertility ,Evolution, Molecular ,Structural variation ,03 medical and health sciences ,single nucleotide polymorphism ,Genetic variation ,Genetic predisposition ,medicine ,Humans ,Review Articles ,Infertility, Male ,030304 developmental biology ,fertility ,Genetics ,spermatogenic failure ,0303 health sciences ,Chromosomes, Human, Y ,030305 genetics & heredity ,structural variation ,medicine.disease ,Reproductive Medicine ,infertility - Abstract
Genetic variation on the Y chromosome is one of the best-documented causes of male infertility, but the genes responsible have still not been identified. This review discusses how an evolutionary perspective may help with interpretation of the data available and suggest novel approaches to identify key genes. Comparison with the chimpanzee Y chromosome indicates that USP9Y is dispensable in apes, but that multiple copies of TSPY1 may have an important role. Comparisons between infertile and control groups in search of genetic susceptibility factors are more complex for the Y chromosome than for the rest of the genome because of population stratification and require unusual levels of confirmation. But the extreme population stratification exhibited by the Y also allows populations particularly suitable for some studies to be identified, such as the partial AZFc deletions common in Northern European populations where further dissection of this complex structural region would be facilitated.
- Published
- 2008
10. Edward Martin (1859-1938). The founding father of modern clinical andrology
- Author
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Anne M. Jequier
- Subjects
Male ,medicine.medical_specialty ,Urology ,Endocrinology, Diabetes and Metabolism ,Obstructive azoospermia ,Semen analysis ,urologic and male genital diseases ,Male infertility ,Andrology ,Sperm movement ,medicine ,Humans ,Ejaculatory duct obstruction ,Spermatogenic failure ,Infertility, Male ,Gynecology ,Azoospermia ,Epididymis ,Philadelphia ,medicine.diagnostic_test ,business.industry ,History, 19th Century ,medicine.disease ,Reproductive Medicine ,General Surgery ,business - Abstract
Summary Edward Martin (1858–1938) was the first surgeon to treat successfully the problem of obstructive azoospermia, a feat that he first described in 1902. He subsequently carried out a total of 11 such operations that resulted in seven patencies and three pregnancies. He also demonstrated that the epididymis was the major site of these obstructive lesions. He pointed out the need for semen analysis in diagnosis and also demonstrated that azoospermia could have two causes, namely spermatogenic failure and ductal obstruction. He also made some important observations on sperm movement. He was probably the first clinician to demonstrate surgically ejaculatory duct obstruction, vasal atrophy and congenital absence of the vas. Most important of all, he demonstrated the need for accurate diagnosis in the treatment of male infertility. An argument is put forward that Edward Martin deserves the title of the ‘Founding Father of Modern Clinical Andrology’.
- Published
- 1991
11. Y chromosome variants and male reproductive function.
- Author
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McElreavey, Ken, Ravel, Celia, Chantot-Bastaraud, Sandra, and Siffroi, Jean-Pierre
- Subjects
Y chromosome ,SEX chromosomes ,HUMAN reproduction ,HUMAN fertility ,MALE infertility ,MALE reproductive organ diseases - Abstract
The detailed analysis of the Y chromosome in men with azoospermia or severe oligozoospermia has resulted in the identification of three regions of the long arm of the human Y chromosome, termed AZFa, AZFb and AZFc, (AZF: AZoospermia Factor) that are currently deleted in men with otherwise unexplained spermatogenic failure. Screening for these deletions is now common in many infertility centres and in some instances they have a prognostic relevance. Recently, attention has turned to partial deletions of the AZFc region. At first sight some of these deletions appear to have little effect on fertility, whilst others appear to be associated with significant risk for developing spermatogenic failure. However, the relationship between these partial AZFc deletions, reduced sperm counts and infertility is the subject of a continuing intense debate. There is a pressing need to clarify the impact of partial AZFc deletions on human spermatogenesis. This requires large-scale studies on well-characterized normospermic and oligo/azoospermic individuals of different ethnic origins with multiple informative AZFc markers if the correlation between these deletions and the phenotype is finally to be resolved. The definition of Y chromosome variants (haplotypes) in cases of partial AZFc deletions is likely to play an essential role in understanding the contribution of the deletion to reduced sperm counts. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
12. XPC gene polymorphisms and risk of idiopathic azoospermia or oligozoospermia in a Chinese population.
- Author
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Jie Liang, Aihua Gu, Yankai Xia, Bin Wu, Ningxia Lu, Wei Wang, Chuncheng Lu, Qian Zheng, Shoulin Wang, and Xinru Wang
- Subjects
GENETIC polymorphisms ,POLYMERASE chain reaction ,DNA polymerases ,COMPLEMENTATION (Genetics) ,HUMAN fertility - Abstract
A retrospective case–control study was carried out in the Han-Chinese population to determine the polymorphisms of xeroderma pigmentosum complementation group C ( XPC) gene on the risk of idiopathic azoospermia or oligozoospermia. The Ala499Val (C>T) and Lys939Gln (A>C) polymorphism of XPC gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism in three groups of infertile men (172 patients of azoospermia, 25 patients of severe oligozoospermia, 55 patients of oligozoospermia) and 228 fertile men. Increased risk of idiopathic azoospermia, but not oligozoospermia was associated with the XPC variant genotypes of Ala499Val (C>T) [adjusted odds ratio (OR) = 1.67, 95% confidence interval (CI) = 1.04–2.68 for CT heterozygote and adjusted OR = 2.03, 95% CI = 1.10–3.75 for TT homozygote] compared with CC homozygous wide-type. The Lys939Gln (A>C) polymorphism was not related to spermatogenic failure. The combined risk alleles analysis and haplotype analysis showed that ORs increased as the number of the risk alleles increased and the 499T-939C haplotype had a significantly increased risk of idiopathic azoospermia (OR = 7.97; 95% CI = 3.51–18.07) compared with other haplotypes. The results suggest that XPC Ala499Val (C>T) polymorphism is correlated with high risk of idiopathic azoospermia in the Han-Chinese population. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
13. Quantification of survivin mRNA in testes of infertile patients and in testicular germ cell tumours: high levels of expression associated with normal spermatogenesis.
- Author
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Weikert, Steffen, Schrader, Mark, Christoph, Frank, Schulze, Wolfgang, Krause, Hans, M&Amp;#x00F6;ller, Markus, and Miller, Kurt
- Subjects
MESSENGER RNA ,INFERTILITY ,GERM cells ,TUMORS ,TESTIS ,GENE expression ,SPERMATOGENESIS - Abstract
Deregulated apoptosis of germ cells may contribute to male infertility as well as malignant transformation. Survivin, an inhibitor of apoptosis (IAP), is overexpressed in all the most common human malignancies, but barely detectable in normal tissues. We used real-time polymerase chain reaction (PCR) to quantify survivin mRNA expression in normal testes ( n = 22), testes with defective spermatogenesis ( n = 26) and testicular germ cell tumours (TGCTs; n = 16). Survivin was expressed at high levels in normal testes. Testicular survivin levels in infertile patients were related inversely to the severity of spermatogenic failure ( p < 0.001), with a lack of expression in most specimens with pre-meiotic spermatogenic arrest and in all those with germ cell aplasia. Lower levels of expression were observed in TGCTs than in normal testes. While survivin expression was detected in most TGCTs with undifferentiated components (12 of 13), it was absent in all mature teratomas ( n = 3). These data show that survivin is expressed in normal and transformed germ cells. Its downregulation in spermatogenic disorders indicates that survivin may contribute to the normal balance between germ cell proliferation and apoptosis. In TGCTs, survivin expression appears to be lost with somatic differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
14. Differential effect of specific gr/gr deletion subtypes on spermatogenesis in the Chinese Han population.
- Author
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Yang, Y., Ma, M., Li, L., Su, D., Chen, P., Ma, Y., Liu, Y., Tao, D., Lin, L., and Zhang, S.
- Subjects
SPERMATOGENESIS ,BASIC proteins ,Y chromosome ,OLIGOSPERMIA ,PHENOTYPES - Abstract
As a common variation in the azoospermia factor c ( AZFc) region of Y chromosome, the gr/gr deletion is regarded as a significant risk factor for spermatogenic impairment, whereas the association of the deletion’s phenotypic expression with Y-chromosomal background is still a subject of debate. To further investigate the contribution of the deletion to spermatogenic impairment in different Y-chromosomal haplogroups, the partial AZFc deletion was detected with AZFc-specific sequence tagged sites, gene dosage and gene copy analyses of deleted in azoospermia ( DAZ), chromodomain Y1 ( CDY1) and basic protein Y2 ( BPY2) in 1426 azoo/oligozoospermic and 672 normozoospermic men from a Chinese population. The haplogrouping was performed in 231 deletion carriers with 12 polymorphic loci of Y chromosome. As a result, five gr/gr rearrangement types in eight Y haplogroups were observed, in which the simple gr/gr deletion was the most common type, and its frequency was significantly higher in men with azoo/oligozoospermia relative to normozoospermia. Also the distribution of gr/gr-rearranged Y haplogroups was significantly different between the two groups, in which gr/gr-deleted haplogroups C and DE were more common in men with azoo/oligozoospermia. In the 6 gr/gr copy deletion haplotypes, the frequencies of DAZ1/DAZ2+CDY1a or CDY1b deletion were significantly higher in men with azoo/oligozoospermia, while all DAZ3/DAZ4+CDY1b+BPY2.2 or 2.3 deletions were found only in haplogroup Q1 without any distribution difference between the azoo/oligozoospermic and normozoospermic groups. This study provided further evidence for the existence of multiple subtypes of gr/gr deletion and indicates that gr/gr- DAZ1/DAZ2 deletion is a significant risk factor. However, the association of the phenotypic variation of gr/gr deletion with Y-chromosomal haplogroups is not definite yet, because of the limited amounts of the deletions observed in each of the haplogroups and the lack of the quantitative trait analyses such as sperm density analysis. The fact that a common gr/gr copy deletion haplotype was found exclusively in the Y hgr Q1, without pathogenic consequences, implies the importance of haplogrouping and of copy deletion typing prior to genetic counselling of deletion carriers of Chinese descent. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
15. Massive deletion in AZFb/b+ c and azoospermia with Sertoli cell only and/or maturation arrest.
- Author
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Yang, Y., Ma, M. Y., Xiao, C. Y., Li, L., Li, S. W., and Zhang, S. Z.
- Subjects
SERTOLI cells ,Y chromosome ,MOLECULAR genetics ,SPERMATOGENESIS ,SEX chromosomes - Abstract
Recent studies have revealed that AZF deletion in Y chromosome is the most common known molecular genetic cause of spermatogenetic failure leading to male infertility. Characteristics of AZFa, AZFb and AZFc deletions and their association with spermatogenic impairment have been reported in a large number of populations. However, the distributions of those larger deletions resulted from P5/proximal-P1, P5/distal-P1 and P4/distal-P1 recombinations are still unclear as the literature on their frequencies is limited, and the contribution of these deletions to spermatogenetic failure remain to be confirmed by population studies. In this study, we investigated such massive deletions in 387 idiopathic azoospermic, 269 oligozoospermic patients and 315 men with normal spermatogenesis using 21 AZFb/c specific sequence-tagged sites. As a result, nine uninterrupted massive deletions were observed exclusively in men with azoospermia caused by either Sertoli cell only (SCO) or maturation arrest (MA). Prevalence of the deletion was 2.33%, in which five deletions arose from non-allelic homologous recombination between the palindromes P5 and P1 and two between P4 and P1. In other two deletions, novel proximal breakpoints in the interval region between P4 and P3 were observed. Our findings strongly support that the massive deletions in the AZFb or AZFb+ c regions are important genetic causes of SCO and/or MA resulting in azoospermia and, besides the P5/proximal-P1, P5/distal-P1 and P4/distal-P1 deletions there may be other massive deletions in these regions resulting in severe spermatogenic impairment. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
16. Reproductive health problems: genetics vs. environment.
- Author
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Page, D. and Kretser, D.
- Subjects
GENETICS ,REPRODUCTIVE health ,GENOTYPE-environment interaction ,PHENOTYPES ,ENDOCRINE system ,Y chromosome - Abstract
The article presents views of experts on the role of genetics in reproductive health concerns. D. de Kretser encouraged the evaluation of the influence of genotype in the exposure to environmental endocrine disrupters. D. Page claimed the need of considering observations when assessing the role of genetic factors and their interaction with the environment for endocrine disruption. K. McElreavey hypothesized the existence of genes in the Y chromosome which can compensate gene deletions.
- Published
- 2006
- Full Text
- View/download PDF
17. Y chromosome variants and male reproductive function
- Author
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Jean-Pierre Siffroi, Célia Ravel, Sandra Chantot-Bastaraud, and Ken McElreavey
- Subjects
Male ,Azoospermia ,Genetics ,Infertility ,Azoospermia factor ,Chromosomes, Human, Y ,Urology ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,Haplotype ,Genetic Variation ,Fertility ,Oligospermia ,Biology ,Y chromosome ,medicine.disease ,Haplogroup ,Male infertility ,Haplotypes ,Reproductive Medicine ,medicine ,Humans ,Chromosome Deletion ,Infertility, Male ,media_common - Abstract
The detailed analysis of the Y chromosome in men with azoospermia or severe oligozoospermia has resulted in the identification of three regions of the long arm of the human Y chromosome, termed AZFa, AZFb and AZFc, (AZF: AZoospermia Factor) that are currently deleted in men with otherwise unexplained spermatogenic failure. Screening for these deletions is now common in many infertility centres and in some instances they have a prognostic relevance. Recently, attention has turned to partial deletions of the AZFc region. At first sight some of these deletions appear to have little effect on fertility, whilst others appear to be associated with significant risk for developing spermatogenic failure. However, the relationship between these partial AZFc deletions, reduced sperm counts and infertility is the subject of a continuing intense debate. There is a pressing need to clarify the impact of partial AZFc deletions on human spermatogenesis. This requires large-scale studies on well-characterized normospermic and oligo/azoospermic individuals of different ethnic origins with multiple informative AZFc markers if the correlation between these deletions and the phenotype is finally to be resolved. The definition of Y chromosome variants (haplotypes) in cases of partial AZFc deletions is likely to play an essential role in understanding the contribution of the deletion to reduced sperm counts.
- Published
- 2006
18. Subject Index.
- Subjects
PERIODICAL indexes ,ANDROLOGY - Abstract
Presents the subject index for the December 2004 issue of the "International Journal of Andrology."
- Published
- 2004
- Full Text
- View/download PDF
19. Novel mutations in calcium/calmodulin-dependent protein kinase IV ( CAMK4) gene in infertile men.
- Author
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Khattri, A., Reddy, V. P., Pandey, R. K., Sudhakar, D. V. S., Gupta, N. J., Chakravarty, B. N., Deenadayal, M., Singh, L., and Thangaraj, K.
- Subjects
PROTEIN kinases ,MALE infertility ,CALMODULIN ,CALCIUM ,SPERMATOGENESIS ,GENETIC polymorphisms ,NUCLEOTIDES - Abstract
Calcium/calmodulin-dependent protein kinase IV (CAMK4) is a multifunctional serine/threonine protein kinase, which plays an important role in the spermatogenesis by phosphorylating protamines. It has been shown to be involved in the regulation of human sperm motility. Moreover, the Camk4 knockout mice were infertile because of severely reduced sperm count and morphological abnormalities. As no study is available on the association of this gene with male infertility, we analysed all the exons of CAMK4 gene in ethnically matched 283 infertile and 268 fertile Indian men. We identified twenty nucleotide substitutions, of which twelve were novel. Of these novel variants, eight were exclusively detected in infertile men. Moreover, two infertile men-specific mutations were non-synonymous replacing amino acids at the highly conserved region. In silico analysis predicted both of these mutations as 'deleterious'. In addition to nucleotide substitutions, we identified five novel insertion-deletion mutations; of these, g.150264_66delGCG was exclusively found in two oligoasthenoteratozoospermic men. In silico analysis of infertile men exclusive mutations predicted that they can alter/diminish the potential binding sites of splicing factors, which may affect the mRNA splicing and protein translation. Our study suggests that the mutations in CAMK4 may lead to abnormal semen parameters. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
20. The role of asynapsis in human spermatocyte failure.
- Author
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Sciurano, R. B., Rahn, M. I., Rey-Valzacchi, G., Coco, R., and Solari, A. J.
- Subjects
BIOMOLECULES ,CHROMOSOMES ,ELECTRON microscopy ,CLINICAL pathology ,CELL nuclei - Abstract
The basic molecular mechanisms by which chromosomal rearrangements in heterozygous state produce spermatogenic disturbances are poorly understood. Testicular biopsies from five patients - one carrier of a Robertsonian translocation rob t(13;14), two carriers of two different Y-autosome translocations, a t(Y;6) and a t(Y;11), one carrier of a reciprocal translocation t(3;13) and one carrier of a heterochromatin duplication in chromosome 9 - were processed for histopathological analysis, electron microscopy and fluorescent immunolocalization of meiotic proteins. In all the patients, the asynaptic regions during pachytene are labelled by BRCA1 and retained RAD51 foci. The variant histone γ-H2AX is located on the chromatin domains of the asynaptic regions and the XY body. In contrast, these meiotic proteins are absent in those chromosomal segments that are non-homologously synapsed. The present observations on five new cases and a review of recent studies show that the common features shared by all these cases are the abnormal location of some meiotic proteins and the presence of transcriptionally silenced chromatin domains on asynaptic regions. The frequent association of these silenced regions with the XY body and the rescue of spermatocyte viability through non-homologous synapsis are also shared by all these carriers. A passive, random mechanism of clustering of asynaptic regions with the XY body is suggested. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
21. Early onset of primary hypogonadism revealed by serum anti-Müllerian hormone determination during infancy and childhood in trisomy 21.
- Author
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Grinspon, R. P., Bedecarrás, P., Ballerini, M. G., Iñiguez, G., Rocha, A., Mantovani Rodrigues Resende, E. A., Brito, V. N., Milani, C., Figueroa Gacitúa, V., Chiesa, A., Keselman, A., Gottlieb, S., Borges, M. F., Ropelato, M. G., Picard, J.-Y., Codner, E., and Rey, R. A.
- Subjects
ANEUPLOIDY ,SEX chromosomes ,HYPOGONADISM ,SPERMATOZOA ,TESTOSTERONE ,LEYDIG cells ,CRYPTORCHISM - Abstract
Summary Male patients with an extra sex chromosome or autosome are expected to present primary hypogonadism at puberty owing to meiotic germ-cell failure. Scarce information is available on trisomy 21, a frequent autosomal aneuploidy. Our objective was to assess whether trisomy 21 presents with pubertal-onset, germ-cell specific, primary hypogonadism in males, or whether the hypogonadism is established earlier and affects other testicular cell populations. We assessed the functional status of the pituitary-testicular axis, especially Sertoli cell function, in 117 boys with trisomy 21 (ages: 2 months-20 year). To compare with an adequate control population, we established reference levels for serum anti-Müllerian hormone (AMH) in 421 normal males, from birth to adulthood, using a recently developed ultrasensitive assay. In trisomy 21, AMH was lower than normal, indicating Sertoli cell dysfunction, from early infancy, independently of the existence of cryptorchidism. The overall prevalence rate of AMH below the 3rd percentile was 64.3% in infants with trisomy 21. Follicle-stimulating hormone was elevated in patients <6 months and after pubertal onset. Testosterone was within the normal range, but luteinizing hormone was elevated in most patients <6 months and after pubertal onset, indicating a mild Leydig cell dysfunction. We conclude that in trisomy 21, primary hypogonadism involves a combined dysfunction of Sertoli and Leydig cells, which can be observed independently of cryptorchidism soon after birth, thus prompting the search for new hypotheses to explain the pathophysiology of gonadal dysfunction in autosomal trisomy. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
22. Identification and characterization of a novel Rab GTPase-activating protein in spermatids.
- Author
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Lin, Y.-H., Lin, Y.-M., Kuo, Y.-C., Wang, Y.-Y., and Kuo, P.-L.
- Subjects
MICROARRAY technology ,IMMUNOFLUORESCENCE ,GERM cells ,SPERMIOGENESIS in animals ,TESTIS abnormalities ,HUMAN fertility - Abstract
Summary We have previously identified novel testis-specific genes by microarray analysis of human testicular tissues. One of the novel genes is Male Germ Cells Rab GTPase- Activating Proteins ( MgcRabGAP), which is characterized by the conserved RabGAP catalytic domain, TBC (Tre2/Bub2/Cdc16). RabGAPs are involved in various physiological processes (e.g. vesicular trafficking, cytoskeletal remodelling, cell migration, etc.) by inactivating Rab proteins. In this study, we found that MgcRabGAP transcripts are mainly expressed in the mouse and human testes. The MgcRabGAP protein is expressed in the elongating and elongated spermatids. Immunofluorescence assay of mouse germ cells showed that the protein expression is enriched at the edge of the acrosomal region, neck and annulus during spermiogenesis. This MgcRabGAP is co-localized with its candidate substrate Rab3A at the acrosome/acroplaxome and neck regions of spermatids. Meanwhile, MgcRabGAP is co-localized and interacts with β-actin. In humans, the expression of MgcRabGAP is enriched at the stage of elongating spermatids. The amount of MGCRABGAP transcript is reduced in the testicular tissues of men with various types of spermatogenic defects. Considering that MGCRABGAP is exclusively expressed in post-meiotic male germ cells, the decreased transcript amount may be a phenomenon secondary to loss of germ cells in the testicular samples. Our finding strongly suggests that MgcRabGAP is involved in acrosome/acroplaxome formation and cytoskeletal reorganization via Rab activity during mammalian spermiogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
23. A rare Y chromosome constitutional rearrangement: a partial AZFb deletion and duplication within chromosome Yp in an infertile man with severe oligoasthenoteratozoospermia.
- Author
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Shi, Y.-C., Cui, Y.-X., Zhou, Y.-C., Wei, L., Jiang, H.-T., Xia, X.-Y., Lu, H.-Y., Wang, H.-Y., Shang, X.-J., Zhu, W.-M., Li, X.-J., and Huang, Y.-F.
- Subjects
Y chromosome ,LUTEINIZING hormone ,KARYOTYPES ,SPERMATOGENESIS ,OLIGOSPERMIA ,SPERMATOZOA - Abstract
Summary We report a case of an infertile man with severe oligoasthenoteratozoospermia with a partial azoospermia factor b (AZFb) deletion and duplication region within chromosome Yp11.2. The hormonal profile was normal for serum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone and oestradiol. The patient, who showed a 46,XY karyotype, had an approximate 2.4 Mb inherited duplication region in Yp11.2 and a de novo partial AZFb deletion, which spanned 5.25 Mb including eight protein coding genes and four non-coding transcripts, but did not remove the RBMY gene family. Both proximal and distal breakpoints of the deletion were outside any palindromic region or inverted repeat sequence and intra-chromosomal non-allelic homologous recombination could not have been the deletion mechanism. The partial AZFb deletion in our case diminished sperm production, but did not completely extinguish spermatogenesis. Considering severe oligozoospermia, spermatozoa in the patient's ejaculate were used for intracytoplasmic sperm injection, resulting in two twin pregnancies. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
24. Polymorphisms, haplotypes and mutations in the protamine 1 and 2 genes.
- Author
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Jodar, M., Oriola, J., Mestre, G., Castillo, J., Giwercman, A., Vidal-Taboada, J. M., Ballescà, J. L., and Oliva, R.
- Subjects
GENETIC polymorphisms ,GENETIC mutation ,PROTAMINES ,MALE infertility ,SPERMATOZOA ,CHROMATIN - Abstract
Summary Protamines are the most abundant nuclear proteins and alterations in their expression have been described in infertile patients. Also, protamine haplo-insufficient mice have been described as infertile. Therefore, the protamine 1 and 2 genes have been considered important candidates in different mutational studies. In this article, we review all published articles related to protamine gene mutations and report new data on mutations from patients and controls drawn from the Spanish and Swedish populations. Sequencing of the protamine 1 and 2 genes in a total of 209 infertile patients and 152 fertility-proven controls from the Spanish and Swedish populations identified two novel and rare non-pathogenic missense mutations (R17C and R38M) in the protamine 1 gene and several additional polymorphisms. Furthermore, we have identified and we report for the first time five novel rare haplotypes encompassing the protamine 1 and 2 genes. A review of all available protamine gene mutational studies indicates that none of the reported missense mutations can be considered of proven pathogenicity. However, it is interesting to note that rare protamine 1 promoter variants have been reported only in infertile patients, but not in fertile control groups. Pathogenic high penetrance protamine gene missense mutations, if any, must be extremely rare. However, the detected presence of rare variants and haplotypes in infertile patients deserves further investigation. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
25. Semen quality in men with Y chromosome aberrations.
- Author
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Antonelli, A., Marcucci, L., Elli, R., Tanzi, N., Paoli, D., Radicioni, A., Lombardo, F., Lenzi, A., and Gandini, L.
- Subjects
SEMEN analysis ,Y chromosome abnormalities ,MALE infertility ,MEIOSIS ,SPERMATOGENESIS ,MEDICAL screening - Abstract
Summary Infertile males sometimes bear structurally balanced chromosome aberrations, such as translocations and inversions, which involve both autosomes and sex chromosomes. The aim of this study was to evaluate genotype-phenotype correlations in a sample of infertile men with various types of Y chromosome abnormalities. In particular, we examined the effect of (i) balanced structural aberrations such as translocations between sex chromosomes and autosomes; (ii) unbalanced structural aberrations such as deletions or isodicentrics, both [idic(Yp)] and [idic(Yq)]. We studied 13 subjects bearing Y chromosome aberrations. Each patient underwent seminal fluid examination, andrological inspection, hormone study, testicular ultrasound, conventional and molecular cytogenetic analysis and study of Y chromosome microdeletions. Comparison of genotype and sperm phenotype in infertile patients with various Y chromosome aberrations revealed the key role of meiotic pairing defects in arresting spermatogenesis, both in the presence and in the absence of azoospermic factor microdeletions and cell mosaicism. The failure of meiosis and, in consequence, spermatogenesis may be a result of the failure to inactivate the X chromosome in the meiotic prophase, which is necessary for normal male spermatogenesis to take place. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
26. Correlation between testicular sperm extraction outcomes and clinical, endocrine and testicular histology parameters in 120 azoospermic men with normal serum FSH levels.
- Author
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Mitchell, V., Robin, G., Boitrelle, F., Massart, P., Marchetti, C., Marcelli, F., and Rigot, J.-M.
- Subjects
FOLLICLE-stimulating hormone ,GLYCOPROTEIN hormones ,PITUITARY hormones ,INHIBIN ,SEX hormones ,SPERMATOZOA - Abstract
Summary [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
27. Genome-wide association studies provide new insights into the genetic basis of testicular germ-cell tumour.
- Author
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Turnbull, C. and Rahman, N.
- Published
- 2011
- Full Text
- View/download PDF
28. The TNP1 haplotype - GCG is associated with azoospermia.
- Author
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Khattri, A., Bhushan, S. S., Sireesha, V., Gupta, N. J., Chakravarty, B. N., Deendayal, M., Prasad, S., Singh, L., and Thangaraj, K.
- Subjects
NUCLEAR proteins ,SOMATIC cells ,HISTONES ,SPERMATOGENESIS ,GENETIC mutation ,GENE expression ,GENETIC polymorphisms ,MALE infertility - Abstract
Transition nuclear proteins (TNP1 and TNP2) are the major nuclear proteins that replace somatic histones during spermatogenesis. TNPs are required for the maintenance of normal spermatogenesis. Moreover, spermatogenesis was found to be compromised in both Tnp1 and Tnp2 null mice. As no study is available on the role of these genes in Indian infertile men, we have sequenced the entire TNP1 and TNP2 genes in 320 infertile men and 280 control fertile men drawn from two states in India. We identified 18 variants, including 8 previously known and 10 novel. Of the 10 novel variants, 3 were found only in azoospermic men, of which 2 (g.-688A>T in TNP1 and g.1030G>A in TNP2) were predicted to affect the transcription factor binding sites and therefore can cause deregulation of gene expression. Haplotype association analysis showed a significant omnibus association (omnibus χ = 7.87, p = 0.0195) for the single nucleotide polymorphisms (SNPs) in the TNP1 gene with azoospermia. The frequency of the haplotype GCG (H3) was increased in azoospermic men (53.1%) compared with fertile men (43%; χ = 7.964, p = 0.005). However, similar analysis of the TNP2 gene did not show any association with infertility. Furthermore, expression analysis of the TNP1 gene in obstructive azoospermic men showed that haplotypes of the TNP1 gene do not affect its expression level. Our results suggest that the individual SNPs of the TNP1 and TNP2 genes are not associated with infertility; however, the haplotype GCG of the TNP1 gene is a risk factor for azoospermia. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
29. Invited Lectures.
- Subjects
ABSTRACTS ,ANDROLOGY ,ANDROGENS ,HUMAN fertility ,MALE infertility - Abstract
The article presents abstracts of studies related to andrology including "Androgen action in the testis," by G. Verhoeven, "Sperm Biology for Andrologists," by R.J. Aitken, and "Genetic testing in infertile males," by C. Krausz.
- Published
- 2010
- Full Text
- View/download PDF
30. Scientific Programme.
- Subjects
PROGRAMS (Printed ephemera) ,ANDROLOGY ,CONFERENCES & conventions - Abstract
The article presents the programme for the 6th European Congress of Andrology, which will be held at the Megaron Athens International Conference Centre in Athens, Greece on September 29 to October 1, 2010.
- Published
- 2010
- Full Text
- View/download PDF
31. Oral Communications.
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ABSTRACTS ,ANDROLOGY ,ANDROGENS ,HUMAN fertility ,SPERMATOZOA - Abstract
The article presents abstracts of studies related to andrology including "Androgen molecular mechanisms involved in regulation of the masculinisation programming window," by A. Dean and colleagues, "Fertility in men with congenital and acquired undescended testes," by J. Van Brakel and colleagues, and "Glutathione peroxidase 5 controls spermatozoa integrity and embryo viability," by E. Chabory and colleagues.
- Published
- 2010
- Full Text
- View/download PDF
32. Poster Presentations.
- Subjects
ABSTRACTS ,ANDROLOGY ,ANDROGENS ,SPERMATOZOA ,LABORATORY rabbits ,SEMEN ,PHYSIOLOGICAL effects of electromagnetism - Abstract
The article presents abstracts of studies related to andrology including "Androgen deficiency and insulin resistance in obese male patients," by S. H. Janjgava and colleagues, "Post-testicular cholesterol homeostasis controls spermatozoa," by A. Ouvrier and colleagues, and "Exposure to a conventional mobile phone may end with azoospermia: a case report in a rabbit model," by N. Salama and colleagues.
- Published
- 2010
- Full Text
- View/download PDF
33. Gonadal dysfunction in male cancer patients before cytotoxic treatment.
- Author
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van Casteren, Niels J., Boellaard, Willem P. A., Romijn, Johannes C., and Dohle, Gert R.
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TESTICULAR cancer ,GONADAL diseases ,CANCER treatment ,CRYOPRESERVATION of organs, tissues, etc. ,INHIBIN ,ANTINEOPLASTIC agents ,ANDROLOGY - Abstract
Male patients diagnosed with cancer are often referred for semen cryopreservation before gonadotoxic treatment but often have low semen quality. The aim of this study was to evaluate which type of cancer affects gonadal function and proposes a risk factor for low pre-treatment semen quality. Between January 1983 and August 2006, 764 male cancer patients were referred for semen cryopreservation prior to chemotherapy and radiotherapy. We compared semen characteristics and reproductive hormones between different groups of cancer patients. In addition, we evaluated the role of tumour markers in patients with testicular germ-cell tumours (TGCT) on fertility. Abnormal semen parameters were found in 489 men (64%) before cancer treatment. Patients with TGCT and extragonadal germ-cell tumours had significantly lower sperm concentrations and inhibin B levels than all other patient groups. No semen could be banked in 93 patients (12.2%). Eight hundred and thirty-nine of 927 (90%) produced semen samples were adequate for cryopreservation. Inhibin B in all groups showed to be the best predictor of semen quality. Although pre-treatment raised tumour markers were associated with a decrease in inhibin B and increased follicle stimulating hormone, both predictive for low semen quality; no direct linear association could be found between raised beta-HCG, alfa-fetoprotein and semen quality. Only 1/3 of cancer patients had normal semen parameters prior to cancer treatment. Patients with TGCT and extragonadal GCT have the highest risk for impaired semen quality and gonadal dysfunction at the time of semen cryopreservation. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
34. CAG repeat variation in the mtDNA polymerase γ is not associated with oligoasthenozoospermia.
- Author
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Rani, Deepa Selvi, Carlus, S. Justin, Poongothai, J., Jyothi, Amara, Pavani, Kadupa, Gupta, Nalini J., Reddy, Alla G., Rajan, M. Mamtha, Rao, Kamini, Chakravarty, Baidyanath, Singh, Lalji, and Thangaraj, Kumarasamy
- Subjects
MALE infertility ,MITOCHONDRIA ,TRINUCLEOTIDE repeats ,DNA polymerases ,DNA replication - Abstract
Variations in the trinucleotide-CAG repeat number of the catalytic subunit of the mitochondrial DNA polymerase gamma (POLG) have been speculated to be associated with male infertility. The ten CAG repeats (10/10) were found to be the most common allele (88%), absence of which was found to be associated with male infertility. As no study on Indian population was conducted so far to support this view, we investigated the distribution of the POLG-CAG repeats in 509 oligoasthenozoospermic and 241 normozoospermic control Indian men from the same ethnic background. Our study suggested that the distribution of common allele (10/10) was almost similar in both infertile (75%) and normozoospermic (75.5%) men. Further, we had analysed the CAG repeat number in as many as 1306 Indian men belonging to different ethnic, geographical and linguistic backgrounds and found the common allele 10/10 at a frequency of 78.4%. Our study, therefore, suggests that the 10-CAG repeat is the most common allele present in Indian populations, but its absence and the occurrence of the other mutant homozygous (non 10/non 10) genotype should not be understood as being specific to infertility. It, thus, suggests that the POLG-CAG repeat variation is not associated with male infertility in Indian populations, and hence is not a useful marker for screening infertile men. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
35. Quantification of seminal germ cells in azoospermia: correlations with testicular histology and TESE outcome.
- Author
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Yeung, C. H., Beiglböck-Karau, L., Luetjens, C. M., Wunsch, A., and Nieschlag, E.
- Subjects
GERM cells ,TESTIS ,MALE ejaculation ,SPERMATOGENESIS ,SPERMATOZOA - Abstract
In the treatment of male infertility by intra-cytoplasmic injection of spermatozoa (ICSI) extracted from testicular tissue (TESE), the high incidence of negative TESE outcome calls for non-invasive prognostic methods. Literature suggests that seminal haploid germ cell detection could be one. For this purpose, a multi-parametric stringent flow cytometric method was applied to 50 TESE patients for the quantification of ejaculated germ cells. Cells from 50 ejaculates were identified and quantified as spermatozoa (HC, highly condensed), round spermatids (1N), primary spermatocytes (SPC) (4N) or diploid cells (2N, including somatic and non-testicular cells) by their DNA and mitochondria staining and laser scatter characteristics, and compared with testicular biopsy histology and TESE outcome. Whereas 96% of patients displayed a diploid peak in the distribution histograms, the HC, 1N and 4N peaks were absent from the majority of samples. In 13 ejaculates, either a HC or 1N or 4N peak, or a combination of these, was discernible. Although seminal germ cell numbers bore no overall association with elongated spermatids (ES) in histology or spermatozoa retrieval in TESE outcome, 4N cells per ejaculate were correlated with the percentage of tubule sections showing SPC as the most advanced germ cells. The incidence of HC peaks was higher in patients showing some ES in histology or sperm retrieval than in the sperm-negative groups. In groups with suspected obstruction showing nearly full spermatogenesis and maximal sperm retrieval, there was no incidence of a HC peak. Germ cell peaks were associated with germ cell degeneration noted in testicular histology. In conclusion, seminal germ cells cannot provide good prognosis for TESE, although their presence could indicate the spermatogenic activity in the testis. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
36. CA repeat and RsaI polymorphisms in ERβ gene are not associated with infertility in Indian men.
- Author
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Khattri, A., Pandey, R. K., Gupta, N. J., Chakravarty, B., Deendayal, M., Singh, L., and Thangaraj, K.
- Subjects
GENETIC polymorphisms ,MALE infertility ,ESTROGEN ,PATIENTS - Abstract
Oestrogen Receptor β (ERβ) gene plays an important role in the regulation of fertility in both males and females. Polymorphism in CA repeat located in the flanking region of ERβ has been shown to be associated with several diseases, but its association with male infertility has not been analysed so far. However, RsaI polymorphism (rs1256049) in exon 5 of ERβ has been shown to be associated with male infertility in Caucasian patients. Hence, we have analysed 695 Indian men, including 443 infertile and 252 fertile men to evaluate the association of CA repeat length and RsaI polymorphisms in male infertility. Our results revealed no significant difference in the distribution of CA repeat length between infertile (mean ± SD 23.24 ± 2.06, median 24) and fertile men (mean ± SD 23.16 ± 2.27, median 24). The analysis of dosage effect by classifying samples into SS (short/short), SL (short/long) and LL (long/long) groups also did not show any significant difference between infertile and fertile men. Similarly, RsaI polymorphism also did not show any significant difference between infertile and fertile men. Furthermore, the combined analysis of CA repeat and RsaI polymorphisms by haplotyping showed that the distribution of haplotypes was not significantly different between fertile and infertile men. Our results suggest that CA repeat length and RsaI polymorphisms in ERβ are not associated with infertility in Indian men. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
37. Poster Presentations.
- Subjects
MALE infertility ,GONADOTROPIN releasing hormone ,MEIOSIS ,MEDICAL research - Abstract
The article presents abstracts on medical topics which include a study on the description of microarchitecture of human sertoli cells and testicularlamina propia in cases of male infertility, a research on the changes in expression of spermatogonia-specific genes during meiotic changes, and the regulation of gonadotropin-releasing hormone (GnRH) expression by androgens and leptins in human GnRH-secreting FNC-B4 neuroblast.
- Published
- 2008
- Full Text
- View/download PDF
38. Abstracts.
- Subjects
ATHEROSCLEROSIS ,CELL transplantation ,HUMAN fertility ,MEDICAL research - Abstract
The article presents abstracts on medical topics which include a study on the protective role of the endogenous testosterone levels in the development of carotid atherosclerosis, a research on the spermatogonial stem cells heterogeneity as shown by germ cell transplantation, and the differences of seminal quality and fertility potential among men from the European countries who took part in an oocyte donation programme.
- Published
- 2008
- Full Text
- View/download PDF
39. Genetic association analysis: a primer on how it works, its strengths and its weaknesses.
- Author
-
Rodriguez-Murillo, Laura and Greenberg, David A.
- Subjects
GENE mapping ,EPISTASIS (Genetics) ,Y chromosome ,SEX chromosomes ,GENETICS - Abstract
Currently, the most used approach to mapping disease genes is the genome wide association study, using large samples of cases and controls and hundreds of thousands of markers spread throughout the genome. This review focuses in explaining how an association study works, its strengths and its weaknesses, and the methods available to analyse the data. Issues related to sample size, genetic effect sizes, epistasis, replication and population stratification are specifically addressed, issues that an investigator must take into account when planning an association study of any complex disease. Finally, we include some special features concerning association studies in the Y chromosome, and we contrast the analysis characteristics of linkage and association. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
40. An evolutionary perspective on Y-chromosomal variation and male infertility.
- Author
-
Tyler-Smith, Chris
- Subjects
- *
HUMAN genetic variation , *MALE infertility , *INFERTILITY , *GENOMES , *POPULATION , *CHROMOSOMES , *GENETICS - Abstract
Genetic variation on the Y chromosome is one of the best-documented causes of male infertility, but the genes responsible have still not been identified. This review discusses how an evolutionary perspective may help with interpretation of the data available and suggest novel approaches to identify key genes. Comparison with the chimpanzee Y chromosome indicates that USP9Y is dispensable in apes, but that multiple copies of TSPY1 may have an important role. Comparisons between infertile and control groups in search of genetic susceptibility factors are more complex for the Y chromosome than for the rest of the genome because of population stratification and require unusual levels of confirmation. But the extreme population stratification exhibited by the Y also allows populations particularly suitable for some studies to be identified, such as the partial AZFc deletions common in Northern European populations where further dissection of this complex structural region would be facilitated. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
41. Effects of altered epididymal sperm transit time on sperm quality.
- Author
-
Fernandez, Carla Dal Bianco, Porto, Elaine Manoela, Arena, Arielle Cristina, and Kempinas, Wilma De Grava
- Subjects
GENETICS of spermatogenesis ,EPIDIDYMIS physiology ,FERTILITY endocrinology ,THERAPEUTIC use of testosterone ,GUANETHIDINE ,FERTILITY ,REPRODUCTIVE technology ,LABORATORY rats - Abstract
The epididymal sperm transit time seems to have an important role in the process of sperm maturation, and it seems that alterations to the transit can harm the process. The aim of the present work was to evaluate the influence of altered sperm transit time through the epididymis on sperm parameters and fertility of rats, as well as the role of testosterone in the alterations. Sprague–Dawley adult male rats were randomly assigned to four different groups and were treated for 12 days: (i) 10 μg/rat/day DES, to accelerate the transit; (ii) 6.25 mg/kg/day guanethidine sulphate, to delay the transit; (iii) same treatment as group 1, plus androgen supplementation; (iv) control animals received the vehicles. Guanethidine treatment delayed the sperm transit time through the epididymal cauda, provoking increased sperm reserves in this region. Animals exposed to DES showed an acceleration of sperm transit time in the epididymis, and consequently decreased sperm density in both epididymal regions, the caput-corpus and cauda, and diminished sperm motility. In both cases sperm production was not altered. Testosterone supplementation was able to restore the transit time to values close to normality, as they were higher than in the control rats. The same occurred in relation to sperm motility. Rats exposed to DES presented lower fertility after in utero artificial insemination using sperm collected from the proximal cauda epididymis. Therefore, it was concluded that the acceleration of rat sperm transit time appeared to harm normal sperm maturation, thus decreasing sperm quality and fertility capacity, in an androgen-dependent way. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
42. The AZF proteins.
- Author
-
Vogt, P. H., Falcao, C. L., Hanstein, R., and Zimmer, J.
- Subjects
GENETICS of spermatogenesis ,INFERTILITY ,CHROMOSOME analysis ,MALE infertility ,CHROMATIN ,MEIOSIS ,GENETICS - Abstract
The azoospermia factor (AZF) locus in Yq11 is now functionally subdivided in three distinct spermatogenesis loci: AZFa, AZFb and AZFc. After knowledge of the complete genomic Y sequence in Yq11, 14 Y genes encoding putatively functional proteins and expressed in human testis are found to be located in one of the three AZF intervals. Therefore, a major question for each infertility clinic performing molecular screening for AZF deletions has now raised concerning the functional contribution of the encoded AZF proteins to human spermatogenesis. Additionally, it has been shown that distinct chromatin regions in Yq11 overlapping with the genomic AZFb and AZFc intervals are probably involved in the pre-meiotic X and Y chromosome pairing process. An old hypothesis on the germ line function of AZF becomes therefore revitalized. It proposed a specific chromatin folding code in Yq11, which controls the condensation cycle of the Y chromosome in the male germ line. Thus, with the exception of AZF proteins functionally expressed during the pre-meiotic differentiation and proliferation of spermatogonia, the need for AZF proteins functionally expressed at meiosis or during the post-meiotic spermatid maturation process is difficult to assess before the identification of specific mutations in the corresponding AZF gene causing male infertility. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
43. Varicocele sclerotherapy improves serum inhibin B levels and seminal parameters.
- Author
-
Di Bisceglie, Cataldo, Bertagna, Angela, Baldi, Matteo, Lanfranco, Fabio, Tagliabue, Milena, Gazzera, Carlo, Gandini, Giovanni, and Manieri, Chiara
- Subjects
VARICOCELE ,SPERMATIC cord diseases ,VARICOSE veins ,SCLEROTHERAPY ,DRUG therapy ,SEROTHERAPY - Abstract
The usefulness of treating varicocele in order to improve fertility is still a matter of debate. The aim of this study was to evaluate variations in seminal parameters and inhibin B concentrations in a group of males affected by varicocele and treated by percutaneous retrograde sclerotherapy in comparison with a group of patients who did not undergo varicocele treatment. Thirty-eight patients with left varicocele underwent spermatic vein phlebography and percutaneous retrograde sclerotherapy with hydroxy-polyaethoxy-dodecanol. Serum inhibin B, follicle-stimulating hormone (FSH), testosterone levels and seminal parameters (sperm concentration, motility and morphology) were performed before and 6 months after sclerotherapy. Forty patients with left varicocele who did not undergo sclerotherapy were studied as controls. A significant increase ( p < 0.01) in serum inhibin B levels and a significant decrease ( p < 0.05) in FSH levels were observed 6 months after treatment. Semen analysis showed a significant improvement in sperm concentration ( p < 0.05) and progressive motility ( p < 0.01) after treatment. In control group no significant variations in hormonal and seminal parameters were observed 6 months after the basal examination. Six months after the basal evaluation, inhibin B levels were significantly higher in treated subjects than in controls ( p < 0.05) whereas FSH levels were significantly lower ( p < 0.05). Sperm concentration and progressive motility were significantly increased ( p < 0.05 and p < 0.001, respectively) in treated subjects in comparison with controls. In conclusion, varicocele sclerotherapy improves inhibin B levels and seminal parameters, confirming the positive effect of this treatment on spermatogenesis and Sertoli cell function. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
44. Susceptibility alleles for testicular germ cell tumour: a review.
- Author
-
Rapley, E.
- Subjects
GERM cells ,TESTICULAR cancer ,DISEASES in men ,DISEASE risk factors ,GENEALOGY ,ANDROLOGY - Abstract
Family history is among the strongest and most consistent of the risk factors for testicular germ cell tumour (TGCT). Brothers of affected cases have an 8- to10-fold relative risk and fathers/sons have a risk between four and sixfold. The familial relative risk of TGCT is higher than for most other cancer types, which rarely exceeds four. The high relative risk suggests that inherited susceptibility to TGCT may account for a substantial fraction of TGCT cases. The search for TGCT susceptibility genes has proven difficult and a recent genome-wide linkage study for TGCT susceptibility loci demonstrated no statistically significant regions of linkage with all LOD scores less than two. Moreover, a previous report of linkage to a region on Xq27 was not replicated. The results from genetic linkage analysis demonstrate that TGCT susceptibility is likely to be due to several genes, each with a modest effect on disease risk. The Y chromosome, which cannot be analysed by genetic linkage, carries a number of testis- and germ cell-specific genes. We recently demonstrated that a deletion on the Y chromosome known as ‘gr/gr’ is a rare, low-penetrance allele that is associated with susceptibility to TGCT. Based on the evidence from the linkage search the ‘gr/gr’ deletion represents one of possibly many TGCT susceptibility alleles, and new and emerging technologies will be employed in future work to identify these genes. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
45. Single nucleotide polymorphisms in succinate dehydrogenase subunits and citrate synthase genes: association results for impaired spermatogenesis.
- Author
-
Bonache, Sandra, Martínez, Juanjo, Fernández, Marlin, Bassas, Lluís, and Larriba, Sara
- Subjects
GENETIC polymorphisms ,SUCCINATE dehydrogenase ,SPERMATOGENESIS ,MALE infertility ,MEN'S health ,GENES - Abstract
Evaluation of the possible implication of the SDHA, SDHB, SDHC, SDHD and CS genes in non-obstructive male infertility was performed on the basis that sperm concentration in the ejaculate has been previously correlated with nuclear-encoded mitochondrial enzyme activities (the four subunits of succinate dehydrogenase/complex II of the respiratory chain and citrate synthase). We performed an exhaustive analysis of the five genes for the presence of sequence variants that could be associated with impairment of sperm production.blastn searches in the genomic sequence NCBI database evidenced the presence of highly homologous sequences elsewhere on the genome that can interfere with polymerase chain reaction experiments. Therefore, a careful design of the analytical strategy to search for sequence variants was performed. In this report, we provide primer sequences that allowed selective amplification of coding and immediate flanking regions of the five genes. Fifty-five sequence variations in the five genes were identified in infertile and normozoospermic fertile individuals as controls and only one of them ( SDHA c.456+32G>A) showed significant genotype association with impairment of sperm production. Moreover, new single nucleotide polymorphisms identified should be useful in future association studies for other human diseases related to nuclear-encoded genes, leading to mitochondrial respiratory chain activity impairment revealing the physiological role of these genes. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
46. XPC gene polymorphisms and risk of idiopathic azoospermia or oligozoospermia in a Chinese population
- Author
-
Liang, Jie, Gu, Aihua, Xia, Yankai, Wu, Bin, Lu, Ningxia, Wang, Wei, Lu, Chuncheng, Zheng, Qian, Wang, Shoulin, and Wang, Xinru
- Published
- 2009
- Full Text
- View/download PDF
47. Molecular evaluation of CFTR sequence variants in male infertility of testicular origin.
- Author
-
Larriba, S., Bonache, S., Sarquella, J., Ramos, M. D., Giménez, J., Bassas, L., and Casals, T.
- Subjects
GENES ,INFERTILITY ,SPERMATOZOA ,GENETIC research ,MALE infertility ,MEN'S health - Abstract
Although the involvement of the CFTR gene has been well established in congenital agenesia of vas deferens, its role in non-obstructive (NOb) infertility is still a matter of debate. In order to definitively define the involvement of the CFTR gene in spermatogenic impairment and a potential synergistic contribution to known genetic and clinical factors, genetic variants in the entire coding sequence and the immediately flanking regions of the CFTR gene, along with a thorough clinical evaluation, were analysed in 83 NOb infertile patients and 87 clinically well-defined fertile individuals as controls. The results of our study showed no statistical difference between CFTR carrier frequency in the infertile and fertile population. Specifically, the IVS8-6(5T) allele carrier frequency was similar in NOb infertile patients when compared with fertile men, but it is noteworthy that, when fertile men were classified into having optimal and suboptimal fertility, no 5T allele was found among the 35 men with optimal fertility parameters. In conclusion, extensive CFTR analysis in infertile individuals and fertile population as adequate control definitively excludes the involvement of the CFTR gene variants in sperm production and stresses the importance of carefully identifying those individuals with obstructive defects, in whom CFTR screening will be beneficial. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
48. Workshops.
- Subjects
MALE reproductive organs ,HUMAN reproduction ,SEMEN ,MALE infertility ,ANDROGENS ,HORMONE therapy - Abstract
Presents abstracts of studies on male reproduction. Semen analysis; Use of radiographic imaging in the evaluation of male infertility; Monitoring of androgen replacement therapy.
- Published
- 2005
- Full Text
- View/download PDF
49. Hormonal regulation of spermatogenesis.
- Author
-
Holdcraft, Robert W. and Braun, Robert E.
- Subjects
HORMONES ,SPERMATOGENESIS ,TESTIS ,PARACRINE mechanisms ,AUTOCRINE mechanisms ,GONADOTROPIN - Abstract
Proper functioning of the mammalian testis is dependent upon an array of hormonal messengers acting through endocrine, paracrine, and autocrine pathways. Within the testis, the primary messengers are the gonadotrophins, follicle stimulating hormone and luteinizing hormone, and the androgens. Abundant evidence indicates that the role of the gonadotrophins is to maintain proper functioning of testicular somatic cells. It is the androgens, primarily testosterone, which act through the somatic cells to regulate germ cell differentiation. Despite extensive research in this area, little is known about the cell-specific requirements for androgens and even less is understood about the downstream effectors of androgen signalling. However, recent work using cell-specific ablation of androgen receptor function has demonstrated a clear requirement for androgen signalling at multiple, discrete time points during spermatogenesis. These models also provide useful tools for identifying the targets of androgen receptor activity. The purpose of this review is to provide a brief overview of recent advances in our understanding of hormonal regulation of spermatogenesis, with an emphasis on the role of testosterone within the testis, and to pose important questions for future research in this field. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
50. EAA/EMQN best practice guidelines for molecular diagnosis of y-chromosomal microdeletions. State of the art 2004.
- Author
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Simoni, M., Bakker, E., and Krausz, C.
- Subjects
Y chromosome ,MOLECULAR diagnosis ,HUMAN chromosome abnormality diagnosis ,MALE infertility ,OLIGOSPERMIA ,MOLECULAR genetics ,ANDROLOGY ,QUALITY control - Abstract
Microdeletions of the Y chromosome are the second most frequent genetic cause of spermatogenetic failure in infertile men after the Klinefelter syndrome. The molecular diagnosis of Y-chromosomal microdeletions is routinely performed in the workup of male infertility in men with azoospermia or severe oligozoospermia. Since 1999, the European Academy of Andrology (EAA) and the European Molecular Genetics Quality Network (EMQN) support the improvement of the quality of the diagnostic assays by publication of the laboratory guidelines for molecular diagnosis of Y-chromosomal microdeletions and by offering external quality assessment trials. The present revision of the 1999 laboratory guidelines summarizes the results of a ‘Best Practice Meeting’ held in Florence (Italy) in October 2003. The basic protocol for microdeletion screening suggested in the 1999 guidelines proved to be very accurate, sensitive and robust. In the light of the recent advance in the knowledge of the Y chromosome sequence and of the mechanism of microdeletion it was agreed that the basic 1999 protocol, based on two multiplex polymerase chain reactions each covering the three AZF regions, is still fully valid and appropriate for accurate diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
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