Y Chromosome gr/gr Subdeletion Is Associated with Lower Semen Quality in Young Men from the General Japanese Population but Not in Fertile Japanese Men1

Abstract

Several case-control studies have investigated whether Y chromosome haplogroups or deletions are associated with spermatogenic failure. However, the relationships between Y chromosome haplogroups or deletions and semen quality in general population have not been elucidated. In this study, we assessed relationships between Y chromosome haplogroups or deletions and semen parameters in 791 fertile Japanese men and 1221 young men from the general Japanese population. We found that the haplogroup D2 (M55 lineage) was significantly associated with lower semen parameters, especially total motile sperm count (P = 0.00051, beta = -0.097), in men from the general population but not in fertile men. In addition, we found that the gr/gr subdeletion was associated with semen quality and in particular, strongly associated with decreased sperm motility (P = 0.00041, beta = -3.14) and total motile sperm count (P = 0.00031, beta = -0.099) in men from the general population but not in fertile men. The combined analysis of fertile Japanese men and men from the general Japanese population showed that the haplogroup D2 (M55 lineage) and the gr/gr subdeletion were strongly associated with reduced sperm motility (P = 0.00056, beta = -2.71, and P = 7.7 × 10(-5), beta = -3.05, respectively) and that haplogroup O2b1 was strongly associated with elevated sperm motility (P = 0.00089, beta = 2.94). These observations add further support for the view that the gr/gr subdeletion diminishes sperm motility that consequently may result in male infertility.

Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men

“…On the other hand, when spermatogenesis activities are depressed, a feedback mechanism comes into effect and in turn elevates LH levels. Previously, we demonstrated that the frequency of haplogroup D2a1 was significantly higher in azoospermia patients compared with the fertile controls (Sato et al, 2013), and haplogroup D2a1 was associated with lower sperm motility and the total motile sperm count (Sato et al, 2014). These findings suggest that because males belonging to haplogroup D2a1 demonstrate low spermatogenesis ability, their LH levels might be higher than males who belong to other haplogroup.…”

“…A few of the subjects in this study have been described in previous reports (Iwamoto et al, 2013a,b;Sato et al, 2014). Briefly, samples in cohort 1 were recruited from university students in three study centers based in the urology departments at university hospitals in Japan (Kawasaki, Kanazawa and Nagasaki), as previously reported (Iwamoto et al, 2013b).…”

“…Briefly, samples in cohort 1 were recruited from university students in three study centers based in the urology departments at university hospitals in Japan (Kawasaki, Kanazawa and Nagasaki), as previously reported (Iwamoto et al, 2013b). In addition, we recruited participants from university students at a study center in Sapporo, as previously reported (Sato et al, 2014). Cohort 2 samples were recruited from the partners of pregnant women who attended obstetric clinics in four cities in Japan (Sapporo, Kanazawa, Osaka and Fukuoka) (Iwamoto et al, 2013a).…”

“…In cohort 2, 35.1% had used medications and 0.8% had thyroid disease or diabetes in cohort 2. The Y chromosomes of all subjects were classified into 16 haplogroups according to the YCC nomenclature (Karafet et al, 2008), using 24 Y chromosome markers as previously described (Sato et al, 2014).…”

“…The Y chromosome plays an important biological role in imparting male characteristics, including sex determination (Sinclair et al, 1990), spermatogenesis (Reijo et al, 1995;Nakahori et al, 1996), and male-specific diseases such as prostate cancer (Stone et al, 1978;Ohnuki et al, 1980;Atkin & Baker, 1985). In addition, there have been reports indicating that there exist associations between Y chromosome haplogroups and male infertility (Kuroki et al, 1999;Krausz et al, 2001;Lu et al, 2007;Yang et al, 2008;Puzuka et al, 2011;Ran et al, 2013;Sato et al, 2013), semen parameters (Sato et al, 2014), and prostate cancer (Ewis et al, 2006;Lindstr€ om et al, 2008;Wang et al, 2012) in some populations, including the Japanese. The Y chromosome haplogroup is also associated with several phenotypes other than male characteristics, including cardiovascular risk (Hiura et al, 2008;Bloomer et al, 2013;Kostrzewa et al, 2013), coronary artery disease (Charchar et al, 2012), lipids (Charchar et al, 2004;Russo et al, 2008), and blood pressure (Charchar et al, 2002).…”