Project Portugal 2030

Summary

The diagnosis of male infertility is a long process and troublesome in about 30% of the cases, in which the underlying cause remains unknown even after all the infertility work-up. Also, the outcome of each patient to the different fertility treatments is extremely variable and it is currently impossible to predict its success for each patient. Therefore, there is a dire unmet need to develop a unique tool to facilitate, manage and speed up the diagnosis, prognosis, and treatment of male infertility. We hypothesize that molecular markers associated with the quality of sperm could be used as efficient biomarkers in the diagnosis and prognosis of male infertility. The recent analysis of the RNA landscape of fertile and infertile men revealed several coding and non-coding RNAs differentially expressed between the groups [17]. The same was observed regarding protein expression, with distinct profiles between fertile men and men with distinct alterations being recognized [9]. In the past years, our team has been dedicated to the identification and characterization of molecular biomarkers to assess semen quality, to be used in the diagnosis and prognosis of male infertility as a complementary method to basic semen analysis [7–12]. Aligned with our previous results, the goal of our proposal is to design a stable panel of biomarkers that can be incorporated in a diagnostic array - FERTI$CAN - to stratify patients with male infertility and predict the success of specific reproductive procedures for each patient according to its medical condition. To accomplish this goal, the following aims are proposed: AIM 1 - Systematically review the available literature and meta-analysis development to identify candidate biomarkers, including proteins and RNAs, with potential for discriminating infertility-related phenotypes and high-quality sperm. AIM 2 - Recruit the participants, characterize the study sample, and design standardized protocols to be used among all the recruitment places. AIM 3 - Validate the biomarkers identified by literature review in healthy/young subjects and donors under infertility-related conditions, recognizing the most promising targets. AIM 4 - Develop a prototype for the validation of the most promising biomarkers recognized in human sperm samples and establish a threshold for each biomarker, to be used to complement basic semen analysis. AIM5 – Analyze, integrate, and disseminate the results and define the most appropriate valorization strategy. The successful completion of this project will result in the generation of a new innovative diagnostic device prototype – FERTI$CAN – which has the potential to be used in the clinical setting to complement traditional semen analysis. This device may have several applications including a) explaining situations of idiopathic infertility, failure in ART, and recurrent pregnancy loss; b) assessing the efficacy of medical interventions and treatments; c) selecting the appropriate ART treatment; d) evaluating the impact of diseases affecting the male reproductive system, and e) monitoring the impact of lifestyle alterations in sperm quality. This new method can be customized, depending on the selected biomarker panel, and adapted to the patient’s clinical history and goal (diagnostic, prognostic, or ART selection). Undoubtedly, our final goal is to improve male fertility diagnosis and treatment by providing a reliable alternative to traditional basic semen analysis.