Understanding the age-related alterations in the testis-specific proteome

ABSTRACT

Introduction

Fertility rates in developing countries have declined over the past decades, and the trend of delayed fatherhood is rising as societies develop. The reasons behind the decline in male fertility with advancing age remain mysterious, making it a compelling and crucial area for further research. However, the limited number of studies dedicated to unraveling this enigma poses a challenge. Thus, our objective is to illuminate some of the upregulated and downregulated mechanisms in the male testis during the aging process.

Areas covered

Herein, we present a critical overview of the studies addressing the alterations of testicular proteome through the aging process, starting from sexually matured young males to end-of-life-expectancy aged males. The comparative studies of the proteomic testicular profile of men with and without spermatogenic impairment are also discussed and key proteins and pathways involved are highlighted.

Expert opinion

The difficulty of making age-comparative studies, especially of advanced-age study subjects, makes this topic of study quite challenging. Another topic worth mentioning is the heterogeneous nature and vast cellular composition of testicular tissue, which makes proteome data interpretation tricky. The cell type sorting and comorbidities testing in the testicular tissue of the studied subjects would help mitigate these problems.

KEYWORDS:

• Testicular tissue
• aging
• Proteomics
• male fertility
• testicular biomarkers

Article highlights

• Male fertility decline with age remains a mystery, but proteomic studies can uncover new insights

• Changes in the testicular proteome can highlight dysregulated pathways from testicular senescence.

• Biological processes upregulated during testis aging are cell death, glycolysis, and blood coagulation.

• Biological processes downregulated during testis aging are related to extracellular matrix organization and assembly.

• Testicular aging-related processes come from the development of varicocele, mitochondrial dysfunction, and oxidative damage.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14789450.2023.2274857

Additional information

Funding

This work was supported by the Fundação para a Ciência e a Tecnologia, I.P under grants [CEECINST/00026/2018], [2022.05444.CEECIND], [UI/BD/150749/2020], [UIDB/50006/2020], [UIDB/00215/2020, and UIDP/00215/2020] to UMIB; [LA/P/0064/2020] to ITR - Laboratory for Integrative and Translational Research in Population Health; [UIDB/04501/2020 and UIDP/04501/2020] to Institute of Biomedicine - iBiMED. The work was co-funded by FEDER through the COMPETE/QREN, FSE/POPH and POCI - COMPETE 2020 (POCI-01-0145-FEDER-007491) funds.