Y chromosome microdeletions in azoospermic patients with Klinefelter's syndrome

Purpose Yq microdeletions are the leading genetic cause of male infertility and its detection is clinically relevant for appropriate genetic counseling. We aimed to determine the prevalence and type of Yq microdeletions, the associated seminal phenotypes and the STS markers that are relevant for its testing in Indian population. Methods Yq microdeletion analysis was carried out in 1,636 infertile cases in our centers. Additional data was collected from published studies in Indian population leading to a total of 3,647 cases. Results In our cohort, 3.4 % (56/1,636) of infertile men had Yq microdeletions. Combining the data from other published studies identified 215/3,647 (5.8 %) infertile individuals to harbor Yq microdeletions; with 6.4 % in azoopsermia, 5.8 % in oligozoospermia and 3.2 % in oligoasthenozoospermia and teratozoospermia cases. No significant differences in the deletion frequencies were observed between idiopathic vs non idiopathic cases (5.8 vs 8.6 % respectively). Deletions of AZFc were at highest frequency (46.6 %) with double deletions most commonly observed in azoospermic subjects. With respect to the STS markers, screening with the six European Academy of Andrology (EAA) markers would miss 3

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Y chromosome microdeletions in infertile men: prevalence, phenotypes and screening markers for the Indian population

Sen

Pasi

Dada

et al. 2013

“…However, it is widely reported that men with KS have higher rates of sex and autosomal aneuploidy [5][6][7][8][9][10][11]. Two approaches on the ability of 47,XXY testes to yield postmeiotic cells exist.…”

Section: Discussionmentioning

confidence: 99%

“…In the other 50 %, no germ cells at all or different stages including post-meiotic cells with no mature figures might be present (KS negative). Although higher rates of sex and autosomal aneuploidy have been reported in positive KS patients [5][6][7][8][9][10][11], most offspring had a normal karyotype [12,13]. To date, only one fetus with the 47,XXY karyotype has been conceived and reduced in the 14th gestational week (from a triplet pregnancy) [14], and two other fetuses have been diagnosed as mosaic 46,XY/47,XXY karyotype by preimplantation genetic diagnosis (PGD) [15].…”

Section: Introductionmentioning

confidence: 99%

Ploidy of spermatogenic cells of men with non-mosaic Klinefelter’s syndrome as measured by a computerized cell scanning system

Komsky-Elbaz

Raziel

Ben‐Ami

et al. 2015

Purpose This study aims to characterize the origin of testicular post-meiotic cells in non-mosaic Klinefelter's syndrome (KS). Methods The study included testicular tissue specimens from 11 non-mosaic KS patients, with (6 positive) and without (5 negative) spermatozoa presence. The obtained testicular cells were affixed and stained for morphology followed by fluorescence in situ hybridization (FISH) for centromeric probes X, Y, and 18. We used a computerized automated cell scanning system that enables simultaneous viewing of morphology and FISH in the same cell. Results A total of 12,387 cells from the positive cases, 11,991 cells from the negative cases, and 1,711 cells from the controls were analyzed. The majority of spermatogonia were 47, XXY in both the positive and negative KS cases (88.9±4.76 % and 90.6±4.58 %) as were primary spermatocytes (76.8±8.14 % and 79.6±7.30 %). The respective rates of secondary spermatocytes and post-meiotic cells (round, elongating spermatids and sperm cells) were 1.1±1.39 % in the positive cases, 2.9±3.33 % in the negative cases, compared to 67.6±6.22 % in the controls (P<0.02). Pairing of both 18 and XY homologous chromosomes in 46,XY primary spermatocytes was 2.5 ±2.31 % and 3.4±2.39 %, respectively, compared to 19.8± 8.95 % in the control group (P<0.02) and in 47,XXY primary spermatocytes in 2.4±3.8 % in the positive group and 3.2± 2.26 % in the negative group. Conclusions This study presents data to indicate that the majority of primary spermatocytes in the testes of non-mosaic KS patients are 47,XXY and could possibly develop into postmeiotic cells.

“…This is particularly notable in the azoospermia factor (AZF) region of the Y chromosome. Recent studies have reported that AZF microdeletions are associated with chromosomal abnormalities, and have suggested that the detection of microdeletions should be performed routinely in all infertile males with Y chromosomal abnormalities [12,20]. Similarly, a large number of genes are involved in the regulation of pre-implantation embryo survival and post-implantation embryonic development [9].…”

Section: Introductionmentioning

confidence: 99%

Chromosomal abnormalities in men with pregestational and gestational infertility in northeast China

Zhang

Wang

et al. 2012

Purpose To detect incidences and the types of chromosomal abnormalities in Chinese men with infertility and determine chromosomal factors association with various phenotypes. Methods Semen analysis and karyotype analysis by G-banding were carried out in 4,659 idiopathic infertile males; additionally, multiplex PCR using nine specific sequence-tagged sites (STSs) was used to detect azoospermia factor (AZF) microdeletions in 412 patients with Y chromosomal abnormalities. Results Male infertility was divided into pregestational infertility, characterized by failure to produce a fertilized ovum, and gestational infertility, characterized by embryo loss after fertilization. The former can result from azoospermia, oligozoospermia or oligoasthenozoospermia syndrome, while the latter is associated with developmental early pregnancy loss, habitual miscarriage and stillbirth. Among 4,659 male patients, 412 (8.84 %) showed abnormal chromosomal karyotypes, including 314 (6.74 %) with sex chromosomal abnormalities and 98 (2.10 %) with autosomal abnormalities. The prevalences of numerical and structural abnormalities among patients with chromosomal abnormalities were 259/412 (62.86 %) and 153/412 (37.14 %), respectively. Furthermore, structural sex chromosomal abnormalities were represented by various phenotypic profiles (46,XX, 47,XYY and 45,X/46, XY), and a prevalence of AZF microdeletions of 19/79 (24.05 %). AZF microdeletions were highly associated with Y chromosomal abnormalities (P=0.018). ConclusionVarious chromosomal abnormalities that result in male infertility could affect spermatogenesis or embryonic development at different levels. Sex chromosomal and autosomal abnormalities were highly associated with pregestational and gestational infertility, respectively. AZF microdeletions may play an important role in lowering the stability of the Y chromosome.