Download High frequency of TTTY2-like gene-related deletions in patients with

A new type of common Y chromosome deletions in patients with idiopathic
oligozoospermia and azoospermia
By Vasiliki Michopoulou
Although reproduction seems to be a simple and natural experience for most
couples, for others conceiving is a very difficult procedure.
Sometimes a cause can be found for a couple's infertility and sometimes this is
treatable and restorable. But in other cases not.
The reasons for infertility can involve one or both partners.
In general, the cause of infertility in about one-third of cases involves only the male,
in about one-third of cases, involves only the female and in the remaining cases, the
cause of infertility involves both the male and female, or no cause can be identified.
For about one in five infertile couples the problem lies solely in the male partner.
In most cases, there are no obvious signs of an infertility problem. Intercourse,
erections and ejaculation will usually happen without difficulty. The quantity and
appearance of the ejaculated semen generally appears normal to the naked eye.
Till now we knew that causes of male infertility may include sperm production
problems, blockage of sperm transport, sperm antibodies, sexual or hormonal
problems. In addition, male infertility involved genetic causes such as deletions in
DNA sequences of the Y chromosome, the chromosome which is responsible for
spermatogenesis and male gender. A new type of rather common Y chromosome
deletions associated with male infertility was recently identified for the first time.
The research results of a team led by Professor Christos Yapijakis investigating 94
Greek men with fertility problems indicate that there is a gene family (TTTY2) which
may play a significant role in spermatogenesis and suggest a possible mechanism of
nonhomologous recombinational events that may cause genomic instability and
ultimately lead to male infertility. TTTY2 genes located on Y chromosome and
expressed in testis are likely to be involved in spermatogenesis.
"In this research, we have shown that a considerable percentage of men with fertility
problems of unknown etiologies (sperm count less than normal values) have deletions
in two members of Y chromosome TTTY2 gene family. Interestingly, some infertile
patients had deletions in both genes, although TTTY2L2A and TTTY2L12A are
located far apart in the long and short arms of Y chromosome, respectively. Our data
provide the first documented evidence of TTTY2-like gene deletions implicated in
spermatogenesis and they imply that additional genetic tests of Y chromosome
deletions is necessary in couples with fertility problems", says Prof. Yapijakis.
The studied cohort of 94 infertile patients was divided into three groups as
following: group A (n = 28) included men with idiopathic moderate oligozoospermia,
group B (n = 34) with idiopathic severe oligozoospermia and azoospermia, and group
C (n = 32) with oligo- and azoospermia of various known etiologies. Using PCR
amplification, Prof. Yapijakis' group screened for deletions associated with two
members of a Y-linked multicopy gene family of unknown function that includes
TTTY2L2A and TTTY2L12A genes at Yq11 and Yp11 loci respectively.
No deletions were detected in group C patients and 50 fertile controls. However, two
patients from group A had deletions in TTTY2L2A (7.1%) and six in TTTY2L12A
(21.4%), whereas from group B, four patients had deletions in TTTY2L2A (11.8%)
and 10 in TTTY2L12A (29.4%). In addition, five patients from both groups A and B
(8%) appeared to have deletions in both studied TTTY2 genes, although these are
located very far apart. "Our data provide the first documented evidence of TTTY2-like
gene deletions implicated in spermatogenesis and they imply that additional genetic
tests of Y chromosome deletions is necessary in couples with fertility problems", adds
Prof. Yapijakis.
Reference:
High frequency of TTTY2-like gene-related deletions in patients with idiopathic
oligozoospermia and azoospermia. Yapijakis C, Serefoglou Z, Papadimitriou K,
Makrinou E. Andrologia 2014. doi: 10.1111/and.12300.