Molecular Mechanisms of Testicular Aging Uncovered by Single Cell Analysis

May 17, 2022

Unique Features of Spermatogenesis

One of the most remarkable contrasts in developmental biology is that between sperm cells and egg cells. Both egg and sperm precursor cells are sequestered early on in embryonic development, protecting them from the many additional divisions that the rest of the somatic cells will undergo and preventing accumulation of any DNA mutations.

Sperm and eggs thus constitute what is called the “germ line,” or the cells whose genetic information will be passed to the next generation. However, females are born with all of their egg cells already formed, while males are born with sperm precursor stem cells. These cells will then differentiate into spermatozoa as needed by the body in a process called spermatogenesis, a process that can be dysregulated by aging and poor health.

How Does Aging Affect Male Reproductive Health?

Though it is well established that male fertility and overall reproductive health declines with age, the molecular mechanism of how this occurs in the testis and sperm precursor cells has been poorly understood. In a recent study by Nie et. al. published in Developmental Cell, the authors performed single-cell RNA sequencing (scRNA-seq) to profile over 44,000 testicular cells from younger and older men.

To uncover the molecular mechanisms at play, the authors separated the testicular cells into subtypes using marker genes unique to each stage of spermatogenesis, from the stem cell precursors to each major developmental stage of the sperm cell. They found that age-related changes to sperm stem cell profiles were minor, but that multiple stages of spermatogenesis were significantly affected, as were the somatic cells of the testis. Cell signaling and inflammatory pathways were the primary dysregulated pathways across cell types.

Correlation of Obesity

Remarkably, the extent of dysregulation of spermatogenesis both correlated with increased age and high body mass index (BMI), a common metric for obesity. BMI only correlated with poor effects on testicular cells in the older cohort, indicating that obesity either exacerbates testicular aging over time or may only start to play a significant role after age-related changes have set in. Either way, the authors not only uncovered candidate molecular mechanisms for dysregulation of spermatogenesis but also potential influences of obesity or other comorbidities on this process.

This study is a powerful application of scRNA-seq and bioinformatics analysis to an understudied process in biology. Without single cell technology and its associated sophisticated analytical pipelines, this would historically have been extremely wet-lab intensive information to uncover. Single cell analyses speed up the research process in the right applications, saving time and resources.

Outsourcing Bioinformatics Analysis

Interpreting single cell RNA-seq data is a challenging computational and bioinformatic task. Outsourcing your bioinformatic analysis to experts like our team at Bridge Informatics helps eliminate common challenges with these projects. Book a free discovery call with us today to discuss your project needs.

Jane Cook, Journalist & Content Writer, Bridge Informatics

Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email or


samples being loaded for PCR

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