Telomere length is an important biomarker in several diseases, including male infertility. A decrease in telomere length has been reported in various diseases, and telomere shortening may occur due to ageing, decreased telomerase activity, oxidative stress, or cell division. In recent years, several studies have indicated that infertile men have shorter sperm telomere lengths than fertile men. Shortening of sperm telomeres is associated with male infertility through several mechanisms, including sperm apoptosis, decreased motility, low sperm count, chromosome mispairing and movement during meiosis, and failed fertilization.
The aim of this review was to compile current findings on sperm telomere length and to discuss the findings for comparing sperm from infertile men to fertile men. Several studies reported on sperm telomere shortening associated with infertility. Thus, sperm telomere length can be used as a biomarker for the diagnosis and prognosis of male infertility, since fertile men have longer telomeres and their length decreases with age. However, there is no specific telomere length that is set as a standard/recommended length.
Telomere length in sperm
While women are born with a certain number of oocytes for the rest of their lives, in men spermatogenesis is a dynamic and continuous process from puberty until death. Sperm develop from spermatogonial stem cells in the seminiferous tubules of the testes after one mitotic and two meiotic divisions. The male testicles produce millions of spermatozoa daily, and spermatogenesis takes between 74 and 120 days to complete.
Although telomere length varies between different cells and organs, it is well known that human germ cells have longer telomeres than human somatic cells. It is a paradox that sperm telomeres, despite being longer, appear to lengthen with age compared to somatic cells, and the exact mechanisms of this process remain unclear. One explanation is that molecular resistance against the ageing process may be genetically programmed and since approximately 100 million sperm are produced daily, special telomere maintenance mechanisms are required to prevent rapid telomere shortening.
In this regard, it has been reported that there is high telomerase activity in the testis, leading to the gradual and progressive lengthening of sperm telomeres with age, rather than simply maintaining a stable length. This could mean that telomerase expression favours long telomeres over shorter ones, which is not true, based on studies reporting that, in general, telomerase preferentially lengthens shorter telomeres. Therefore, a plausible explanation is that sperm stem cells with shorter telomeres die disproportionately with age, as a selective cellular process for the maintenance of telomere length.
This is supported by the fact that, according to a series of studies, for each additional year of paternal age at birth, an increase of 17.7 bp is observed in the telomere length of leukocytes and spermatozoa. of the offspring. Despite this fact, however, children of older parents inherit longer telomeres; the older the father, the greater the danger of spontaneous germ cell mutations and, as a consequence, of rare diseases in the offspring, such as achondroplasia and craniosynostosis. This is due to the greater number of replication cycles in terms of spermatogenesis, which corresponds to a greater possibility of an error during this process.
Role of sperm telomeres in the diagnosis and prognosis of male infertility
Despite the variation in sperm telomere length between individuals, it can provide insight into male infertility. As already mentioned, previous studies have indicated that the sperm telomere length of fertile men is significantly longer compared to that of infertile men. Therefore, sperm telomere length can provide information about male fertility, as a shortened telomere can be an indication of impaired spermatogenesis, which can lead to low sperm count, chromosome segregation errors and unbalanced gametes. Additionally, another study reported a strong association between sperm telomere length and sperm count; that is, men with longer sperm telomeres tend to have a good sperm count than those with shorter sperm telomeres.
However, the role of short sperm telomeres (TL) in infertility remains under investigation. If the age factor and other systemic pathologies that affect telomere length are removed from the parameters of a study, it appears that men with oligozoospermia, unlike those who are normozoospermic, have shorter telomere sperm length. Furthermore, men with idiopathic infertility have a shorter sperm telomere length, despite being normozoospermic, compared to fertile men. Since sperm telomere length is strongly associated with sperm count, motility, and decreased DNA fragmentation, sperm telomeres can be used as biomarkers for the diagnosis and prognosis of male infertility.
Importantly, sperm telomere length can also be used to assess sperm quality during assisted reproductive techniques (ART), suggesting that it can be used as one of the criteria for sperm selection during assisted reproductive techniques (ART). the ART. For example, according to previous research, oligozoospermic males with a shorter sperm telomere length pass on a shorter telomere length to their offspring. Therefore, although determining the outcome of infertility treatment is generally based on the ability to conceive or have a child, semen quality, also based on sperm telomere length, can be used as a parameter to estimate the effectiveness of treatment.
Male infertility accounts for approximately half of the total number of infertility cases. So far, the analysis of semen parameters is the most widely used method for the diagnosis of male infertility, as well as for determining the outcome of the medication (ie, the success of the treatment). However, this method cannot be used for infertile men with normal semen parameters. Therefore, the use of sperm telomere length may be relevant for both diagnosis and prognosis of idiopathic infertility.