Screening for deletions in interval D16–22 of the Y chromosome in azoospermic and oligozoospermic Japanese men

Abstract

The genetic basis of infertility remains unclear in a majority of infertile men. In this study, the Y chromosome long arm involving the DAZ (deleted in azoospermia) gene was screened in order to evaluate the occurrence of microdeletion in Japanese infertile men. One hundred and fifty-seven infertile Japanese men with azoospermia and oligozoospermia were analyzed for microdeletions in interval D16-22 of the Y chromosome, using polymerase chain reaction with sequence-tagged site markers. Sixteen sets of oligonucleotide primers were synthesized for the polymerase chain reaction, and Southern blot analysis was also performed. The men were divided into five categories on the basis of sperm concentration: functional azoospermia (A; n ϭ 24), azoospermia caused by obstruction (AO; n ϭ 20), oligozoospermia I (OI, sperm concentration less than 1 ϫ 10 5 /ml; n ϭ 33), oligozoospermia II (OII, sperm concentration less than 1 ϫ 10 6 /ml; n ϭ 30), and oligozoospermia III (OIII, sperm concentration less than 1 ϫ 10 7 /ml; n ϭ 50). Thirty fertile men with a sperm concentration of more than 2 ϫ 10 7 /ml were also analyzed as controls. Microdeletions were identified, in 12 (7.6%) of the 157 infertile men, as follows: 1 man in category A, 1 in category AO, 5 in category OI, 4 in category OII, and 1 in category OIII. No deletion was identified in the fertile men. One common region around sY240 was identified in 11 of the infertile men with microdeletions. This locus may contain specific genes for spermatogenesis. The sperm concentration in the ten oligozoospermic men with microdeletions was below 1 ϫ 10 6 /ml. There were no correlations between the severity of spermatogenic defects and the extent of the microdeletions. These results suggested that genes in the interval D16-22 of the Y chromosome might have important roles in spermatogenesis.

Loss of the AZFc region due to a human Y-chromosome microdeletion in infertile male patients

“…Thangaraj et al (2003) also observed the same frequency of AZFc (3.5%) in azoospermic patients in the Indian population. The changes in the prevalence are due to either small sample size or endocrine disorders, or an unknown environmental factor may be important in influencing the frequency, as has also been documented in different populations of male infertility (Chiang et al, 2000;Kato et al, 2001;Madgar et al, 2002;Sawai et al, 2002;Tse et al, 2002). In the Caucasian population, the frequency of Y-chromosome microdeletion is small; 1% (Pryor et al, 1997) and 3% (Osterlund et al, 2000) have been reported in the Swedish population and 20% in the New Zealand population (Kerr et al, 2000).…”

Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y chromosome in 1,306 infertile Korean men

“…Moreover, about 10% to 15% of idiopathic cases of azoospermia and severe oligozoospermia have microdeletions in AZF regions as the etiologic factor [12][13][14]. The frequency of Y chromosome microdeletions varies between 1% [15] and 55% [16] in the worldwide whereas the few studies performed in Asian male populations showed frequencies of 7.6% to 16.5% in Japan [17][18][19][20][21][22], 11.0% to 19.4% in China [23,24], 10.6% to 11.7% in Taiwan [25,26], 6.4% in Hong Kong [27] and 2.0% to 12.0% in India [12,28,29]. A recently published study reported that the cumulative frequency of Y chromosome microdeletions was 3.5 % in infertile males [30].…”

Transmission of Y chromosomal microdeletions from father to son through intracytoplasmic sperm injection

“…In particular, close relationships between microdeletions in the Y chromosome and spermatogenic failure have been reported (Pryor et al 1997;Kostiner et al 1998;Vogt 1998;McElreavey and Krausz 1999;Foresta et al 2001;Kato et al 2001;Kleiman et al 2001;Simoni 2001). About 10% of infertile males with azoospermia and oligozoospermia have Y chromosomal microdeletions around the AZF region.…”

“…PCR was performed using 16 sets of primers located in the interval D16-22 of the Y chromosome (sY138, sY233, sY240, sY245, sY277, sY254, sY283, sY255, sY236, sY267, Fig. 1a-c sY272, sY269, sY273, sY158, sY159, and sY160 (Vollrath et al 1992), as described previously (Kato et al 2001). E76 primer (ACACAGAGCAAGGCCA GAAT) and E77 primer (CTTCATGGGCCTGAACT GAT) (Ma et al 1993) were used as positive controls.…”