Infertility is a common medical condition with an estimated prevalence of nearly 15% in the general population. The disorder affects both men and women, while the male factor, exclusive or combined with female abnormalities, contributes to approximately half of all cases.

Fertility rates and sperm counts are dramatically declining in many industrialized countries, presumably due to the changing lifestyles and environmental factors. In the Nordic countries, as many as 5% of children are currently born with the use of assisted reproductive technologies. Male infertility is thus a recognized issue and deserves much more scientific and clinical attention.

TEX101 protein

In our research, we focus on categories of male infertility with the reduced amounts of sperm in semen. Such categories range from the lowered production of sperm to severe cases of complete lack of sperm in semen. We previously discovered that low levels of TEX101, a testis-specific protein, in semen could indicate a blockage of sperm transport due to inborn defects, genetic reasons or vasectomy procedures.

Low levels of TEX101, a testis-specific protein, in semen could indicate a blockage of sperm transport due to inborn defects, genetic reasons or vasectomy procedures.

We also suggested that due to its exclusive production in male germ cells, TEX101 protein could serve as an indicator of spermatogenesis in other categories of male infertility. An indicator such as this could predict the whole gradient of male fertility conditions ranging from the complete lack of active spermatogenesis (for example, in the case of Sertoli Cell-Only syndrome) to reduced spermatogenesis and to normal healthy spermatogenesis.

We initially discovered and characterized TEX101 protein by mass spectrometry, a technique suitable for research studies but not for routine measurements in the clinical laboratories. To translate TEX101 biomarker into clinic, we thus developed a simple enzyme-linked immunosorbent assay (ELISA).

Novel diagnostic tests should be thoroughly evaluated prior to their use in the clinic, this was the objective of our present study. We investigated clinical performance of our TEX101 ELISA test in a large cohort of 805 fertile, sub-fertile and infertile men and confirmed three distinct clinical utilities: (i) distinguishing of azoospermia forms; (ii) prediction of the chance of sperm retrieval by surgery; and (iii) evaluation of vasectomy success (vasectomy is a surgical procedure used for male sterilization).

Benefits TEX101 test

Currently the only reliable method to distinguish between azoospermia forms and predict the chance of surgical sperm retrieval is a preliminary diagnostic testicular biopsy, in which a small part of testicular tissue is extracted and investigated under the microscope.

Elimination of the need for invasive diagnostic biopsies is a significant advantage offered by our test and will be welcomed by patients and clinicians. We would thus suggest that TEX101 test is to be offered after the standard protocols for the initial evaluation of infertility (semen analysis and measurement of motility, morphology and levels of reproductive hormones) in patients admitted to the urology clinics, but prior to diagnostic testicular biopsies.

Elimination of the need for invasive diagnostic biopsies is a significant advantage offered by our test and will be welcomed by patients and clinicians.

Our test is simple and inexpensive; it replaces invasive surgical procedures and may facilitate better planning for assisted reproduction. In addition, TEX101 is a protein essential for male fertility, so understanding its functional role and tweaking its activity or concentration might aid the development of effective male contraceptives. We will focus our future efforts on validation of our test by multiple fertility clinics, obtaining regulatory approvals and better understanding of TEX101 biology.

Finally, it should also be emphasized that TEX101 may be among the first protein biomarkers discovered by proteomic technologies. Numerous studies previously attempted to discover disease biomarkers using proteomics and mass spectrometry, but were not able to develop clinically useful protein biomarkers as yet. This resulted in a lot of pessimism in the field of biomarker discovery. Our study may revive the hope to discover disease biomarkers by proteomics and motivate researchers to look for biomarkers of other diseases including major cancers.