Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene

summary Detection of Y-chromosome microdeletion is useful to obtain reliable genetic information for assisted reproductive techniques, thus avoiding unnecessary treatment and vertical transmission of genetic defects. Purposes This research was conducted over a six-year period to analyze clinical data, somatic cytogenetic abnormalities, and types of microdeletions in men with fertility disorders in Iran. Methods and Patients A total of 3654 infertile men were included in this study. Semen samples were analyzed according to standard methods. Conventional chromosomal karyotyping was used to analyze chromosome abnormalities.Polymerase chain reaction (PCR) amplification using nine specific sequence-tagged sites (STS) was used to detect AZF microdeletions. Results Out of the 3654 patients who were analyzed, AZF region microdeletions were detected in 185 cases (5.06 %). Karyotype analysis was available for 157 men and among them abnormal karyotypes were found in 51 cases (32.48 %). One hundred and forty-seven cases with Yq microdeletions suffered from azoospermia and 38 from severe oligozoospermia. Our data show that the most frequent microdeletions were in the AZFc region, followed by the AZFb+c+d, AZFb+c, AZFb, AZFa, and AZF a+c regions. Conclusion The study has confirmed that the detection of microdeletions in the AZF region is significant from a diagnostic viewpoint. It is also useful to obtain reliable genetic information from infertile men to determine the etiology of the deletions, and to avoid unnecessary treatments and vertical transmission of genetic defects.

Section: Discussionmentioning

confidence: 99%

Clinical data for 185 infertile Iranian men with Y-chromosome microdeletion

Totonchi

Meybodi

Boroujeni

et al. 2012

“…The variation in the reported rate is likely caused by the difference in study design and patient cohort selection [4]. The initial cytogenetic observation of an azoospermia factor (AZF) present on Yq was made in 1976, which enabled molecular analysis of Yq microdeletion in infertile men for the first time [5][6][7][8]. Subsequently, the long arm of the Y chromosome was shown to contain three AZF regions, namely AZFa, AZFb, and AZFc, from proximal to distal Yq [8].…”

Section: Introductionmentioning

confidence: 99%

Y chromosome AZFc microdeletion may not affect the outcomes of ICSI for infertile males with fresh ejaculated sperm

Liu

Qiao

et al. 2013

Purpose To explore whether the presence of a Y chromosome AZFc microdeletion confers any adverse effect on the outcomes of intracytoplasmic sperm injection (ICSI) with fresh ejaculated sperm. Methods A total of 143 oligozoospermia patients with Y chromosome AZFc microdeletion in ICSI cycles in a fiveyear period were studied. Infertile men with normal Y chromosome in ICSI at the same time-frame were used as controls matched to the study group for age of female, female's body mass index, male's age, infertility duration and number of oocytes retrieved. Retrospective case-control study was used. Results There were no significant differences between groups in clinical outcomes of endometrial thickness, transferred embryos, good embryo rates, implantation rates, biochemical pregnancy rates, clinical pregnancy rates, ectopic pregnancy rates, miscarriage rates, preterm birth rates, the ratio of male and female babies, newborn body height, newborn weight, low birth weight and birth defects (P>0.05). Patients with Y chromosome AZFc microdeletion had a lower fertilization rate (61.8 % vs. 67.8 %, P<0.05) and higher cleaved embryo rate (94.0 % vs. 88.1 %, P<0.05). Conclusions ICSI clinical outcomes for oligozoospermic patients with Y chromosome AZFc microdeletion are basically comparable to that of infertile patients with normal Y chromosomes. The results of ICSI were not affected by the AZFc deletion. Preimplantation genetic diagnosis (PGD) before ICSI for Y chromosome AZFc microdeletion may not be a justifiable regular procedure if the couples didn't care the vertical transmission of Y chromosome deletion.

“…Molecular and cytogenetic studies from infertile men have shown that microdeletions within the azoospermia factor region (AZF) [5] are prevalent causes of male factor infertility. Analysis of these microdeletions resulted in the identification of three loci in Yq11 involved in the control of spermatogenesis, corresponding to three non-overlapping regions: AZFa, AZFb, AZFc [6][7][8]. About 10-15 % of azoospermia and severe-oligozoospermia patients have microdeletions in AZF region of Y chromosome [9].…”

Section: Introductionmentioning

confidence: 99%

Efficient combined FISH and PRINS technique for detection of DAZ microdeletion in human sperm

Mozdarani

Ghoraeian

2012

Intracytoplasmic sperm injection (ICSI) now offers an effective therapeutic option for men with male infertility and is believed to allow transmission of genetically determined infertility to the male offspring. Transmission of DAZ (Deleted in Azoospermia) microdeletion is one of the major concerns for oligo and severe oligozoospermia patients. Screening of the Y chromosome microdeletion in the diagnostic work-up of infertile men is mainly done using polymerase chain reaction (PCR) on blood leukocytes. However, there are evidences showing that presence of DAZ in somatic cells might not be indicative of its presence in germ cell lineage. In this report we are going to describe a combined Primed in situ labeling (PRINS) and fluorescence in situ hybridization (FISH) technique to show the localization of DAZ gene as well as Y chromosome centromere on sperm nuclei. PRINS is a combination of FISH and in situ polymerization provides another approach for in situ chromosomal detection. In the present study the PRINS primers specific for DAZ genes and traditional direct labeled centromere FISH probes for Y and X chromosomes were used in order to simultaneously detect DAZ genes and sex chromosome aneuploidy in sperm samples.