TTY2 genes deletions as genetic risk factor of male infertility

Abstract

Y chromosome has a number of genes that are expressed in testis and have a role in spermatogenesis. TTY2L12A and TTY2L2A are the members of testis transcript Y2 (TTY2) that are Y linked multi-copy gene families, located on Yp11 and Yq11 loci respectively. The aim of this study was to investigate frequency of TTY2L12A and TTY2L2A deletions in azoospermic patients compared with fertile males. This study was performed on 45 infertile males with idiopathic azoospermia without any AZF micro deletions (group A), 33 infertile males with azoospermia which do not screened for AZF micro deletions (group B) and 65 fertile males (group C), from October 2013 to April 2015 in west of Iran. Polymerase chain reaction (PCR) method was used for detection of TTY2L12A and TTY2L2A gene deletions in studied groups. No deletions were detected in normal fertile males of group C. 1 out of 45 azoospermic males of group A (2.22%) and 3 out of 33 azoospermic males of group B (9.09%) had TTY2L2A deletion (p= 0.409 and p= 0.036 respectively), also 1 out of 45 azoospermic males of group A (2.22%) and 4 out of 33 azoospermic males of group B (12.12%) had TTY2L12A deletion (p= 0.409 and p= 0.011 respectively). None of azoospermic males in Group A and B had deletions in both genes. Our data showed significant correlation between non-obstructive azoospermia and TTY2L12A and TTY2L2A deletions. Thus, it seems that TTY2L12A and TTY2L2A deletions can consider as one of the genetic risk factors for non-obstructive azoospermia.

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“…The authors of this paper also concluded the involvement of these genes in spermatogenesis. With a great surprise a more recent publication reported a very low frequency (about 2.2%) microdeletion for both TTY2L2A and TTY2L12A genes in azoospermia patients with no AZFc microdeletion and higher frequency of microdeletions in azoospermia patients with unkown AZF situation [27]. The frequency of reported microdeletions is much lower and in contradiction with our results (Table 1 and Figure 4) and previous report by Yapijakis et al [26].…”

“…Moreover the deletion in TTY2L12A gene has nothing to do with AZF genes because it is located on the short arm of Y chromosome. Another possibility of lower frequency reported by Shaveisi-Zadeh et al [27] might be related to the studied population with a different ethnicity. However, study of TTY2 gene family is in its early stage.…”

“…Recently other microdeletions of Y chromosome, i.e., TTY2 gene family with a different frequency of occurrence [25] are reported to be involved in male infertility [26,27]. Pseudogene family TTY2 is a Y-linked multicopy gene family with unknown function that includes TTY2L12A and TTY2L2A located at short arm (Yp11) and long arm (Yq11) of Y chromosome respectively [25].…”

The genetic causes of male infertility: a Middle East and North Africa perspective

“…It is important to recognize the genetic basis of infertility to provide better care, as well as an improved prognosis to infertile couples. Several studies have shown how the variation in essential spermatogenesis specific genes led to the impairment of this process and ultimately male infertility (Avenarius et al 2009, Shahid et al 2010, Etem et al 2010, Asadpor et al 2013, Jamshidi et al 2014, Alazami et al 2014, Shaveisi-Zadeh et al 2017, Al-Agha et al 2018, Monsef et al 2018, Akbari et al 2019, Askari, Karamzadeh, et al 2019, Askari, Kordi-Tamandani, et al 2019, Hojati et al 2019, Alimohammadi et al 2020. This section will briefly describe some genes that the deletion or mutation thereof led to impaired male fertility.…”

The genetic causes of male infertility: a Middle East and North Africa perspective

“…It is important to recognize the genetic basis of infertility to provide better care, as well as an improved prognosis to infertile couples. Several studies have shown how the variation in essential spermatogenesis specific genes led to the impairment of this process and ultimately male infertility ( Avenarius et al 2009 , Shahid et al 2010 , Etem et al 2010 , Asadpor et al 2013 , Jamshidi et al 2014 , Alazami et al 2014 , Shaveisi-Zadeh et al 2017 , Al-Agha et al 2018 , Monsef et al 2018 , Akbari et al 2019 , Askari, Karamzadeh, et al 2019 , Askari, Kordi-Tamandani, et al 2019 , Hojati et al 2019 , Alimohammadi et al 2020 ). This section will briefly describe some genes that the deletion or mutation thereof led to impaired male fertility.…”