The Genomics of Puberty

In the first ever genome-scale analysis of the puberty process in humans, researchers have outlined critical changes to stem cells that occur in adolescent males. The researchers believe this study adds to a foundation of knowledge that may yield insights into critical areas of human health, including infertility and cellular changes that lead to cancer and other diseases. The study was published today in Cell Stem Cell.

Puberty introduces monumental changes at a cellular and physiological level in the testis. The testicular cells include spermatogonial stem cells, which ultimately generate sperm production, and niche cells, which help form parts of the testis. In this study, researchers characterized how, just prior to puberty, spermatogonial stem cells expand significantly in number and progress toward meiosis.

Additionally, the study was the first genomic analysis of the testis of adult transfemales (individuals assigned male at birth who identify as female). For these individuals, gender confirmation surgery is preceded by hormone therapy that induces long-term testosterone suppression, enabling the examination of a testis lacking testosterone. By using samples donated after surgery, researchers uncovered critical insights into the role of testosterone in maintaining testis development. Genomic analysis of the cells from the testis of transfemales showed that stem cells and other cells revert to earlier states of development when compared to samples from male adolescents. Thus, testosterone is critical to maintaining the mature state of the testis.

The major changes that occur in humans during puberty give rise to numerous functions in normal development, like reproductive health and fertility. But errors that occur during puberty can result in infertility. The team hopes their insights into how cells develop will lead to a better understanding of developmental issues that result in infertility.

The study also informs understanding of cancer and other diseases that arise due to errors in cellular processes. “The majority of the time, testicular cancers arise when stem cells in the testis are misregulated,” says senior author Bradley Cairns of the University of Utah. “We want to understand how these changes can cause testicular tumors; however, we need to know what should normally happen before we can identify ways to prevent or more effectively treat these cancers.”