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.