Somatic cytogenetic and azoospermia factor gene microdeletion studies in infertile men

Abstract

The objective of the present study was to determine the frequency of somatic chromosomal anomalies and Y chromosomal microdeletions (azoospermia factor genes, AZF) in infertile males who seek assisted reproduction. These studies are very important because the assisted reproduction techniques (mainly intracytoplasmic sperm injection) bypass the natural selection process and some classical chromosomal abnormalities, microdeletions of AZF genes or some deleterious genic mutations could pass through generations. These genetic abnormalities can cause in the offspring of these patients male infertility, ambiguous external genitalia, mental retardation, and other birth defects. We studied 165 infertile men whose infertility was attributable to testicular problems (60 were azoospermic, 100 were oligospermic and 5 were asthenospermic). We studied 100 metaphases per patient with GTG banding obtained from temporary lymphocyte culture for chromosomal abnormality detection and performed a genomic DNA analysis using 28 Y chromosome-specific sequencetagged sites for Y AZF microdeletion detection. Karyotyping revealed somatic anomalies in 16 subjects (16/165 = 9.6%). Of these 16, 12 were in the azoospermic group (12/60 = 20%) and 4 were in the oligospermic group (4/100 = 4%). The most common chromosomal anomaly was Klinefelter syndrome (10/165 = 6%). Microdeletions of AZF genes were detected in 12 subjects (12/160 = 7.5%). The frequencies detected are similar to those described previously. These results show the importance of genetic evaluation of infertile males prior to assisted reproduction. Such evaluation can lead to genetic counseling and, consequently, to primary and secondary prevention of mental retardation and birth defects.

Primary male infertility in Izmir/Turkey: a cytogenetic and molecular study of 187 infertile Turkish patients

“…However no subjects had microdeletions exclusively in the AZFb region in our study, even though they found this to be the second most frequently involved region in their sample of 34 patients (AZFc=79%; AZFb=9%; AZFb/AZFc=6%; AZFa=3%, and AZFa/AZFb/AZFc=3%). Pina-Neto et al also observed similar results in their study [16].…”

Y-chromosome microdeletion and male infertility: a systematic review

“…Studies have good methodological accuracy. The sample universe is quite heterogeneous, given the very design of the studies (22 case reports with 02 individuals up to 33 cross-sectional studies with 4, 441 individuals), age differences between individuals in the samples ranging from 17 years [10] to 66 years [21], as well as the origin of the patients who were: India [2,23,25,35], Brazil [3,31,34,36], China [4,10,17,18], Iran [1,7,19,21] Turkey [5,26,27] [20], Denmark [37], USA [22], england [38], Mexico [30], Serbia [28] and Venezuela [32]. Because of this situation, the data becomes divergent and the comparative analysis becomes troublesome.…”

“…Its etiopathogenesis is not well understood, however, it's known the importance of the role of microdeletion of subregions of the Ychromosome in the casuistry. The literature indicates that deletion of AZF, especially AZFc [12,19,32], is related to azoospermia [1,5,10,18,21,26,31,35], oligozoospermia [10,18,21,31,36] , infertility [4,24] or even normal fertility [7]. The absence of other loci is also underlined by the evidence: AZFa, AZFb, AZFd [10,20,21,23,25,29] and although the prevalence rates are not equidistant.…”

“…Chromosomal variants were found in 8.3%, and Y-chromosome microdeletions in 4.2% of patients. [31] Braz J Med Biol Res 165 infertile men whose infertility was attributable to testicular problems (60 were azoospermic, 100 were oligospermic and 5 were asthenospermic).…”

Efecto de la microdeleción en la región AZF sobre marcadores forenses del cromosoma Y

“…[32] 2006 Brasil 165 hombres infértiles (60 azoospérmicos, 100 oligospérmicos y 5 astenospérmicos) azfc (58,3%), azfb (25%), azfc (25%), azfa (8,3%). [33] 2004 Colombia 97 pacientes infértiles azfc (2,1%) [14] 2003 India 125 hombres infértiles con oligozoospermia y azoospermia y luego 83 citogenética-mente normales 9,63% [34] Fuente: elaboración propia Ambos emplean la técnica de pcr utilizando cebadores específicos para los sts (SequenceTagged Sites) de la región azf. Las zonas sts son secuencias de los extremos de clones largos, usadas para mapeo cromosómico.…”