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ReproUnion supported PhD adds novel insights to how genetic and epigenetic variations influence testicular function

Jun 29, 2021

Infertility affects 15-26% of Danish couples. Male infertility plays a role in approximately half of the cases and a rather large proportion of those are still unexplained.

Male reproduction is complex. It requires strict regulation of hormonal feedback loops as well as proper development of the reproductive organs. Different factors can influence male reproduction at different time points in life, including genetic and environmental factors.

“In my PhD I wanted to investigate the influence of genetic variants on testicular function, and I found that both common and rare genetic variants play different, but significant roles for male reproduction. The common variants, found in many men, had subtle effects, whereas the rarely encountered variants could cause complete arrest of spermatogenesis,” explains Nina Mørup Nygaard, who defended her ReproUnion supported PhD project on the 23rd of April 2021.

Nina Mørup Nygaard found that common genetic variants in a gene called JMJD1C are associated with smaller changes in the level of reproductive hormones and testis size in young Danish men, as well as with the age of pubertal onset in Danish boys. She also identified rare genetic variants causing a block in the production of sperm. The results were published in Scientific Reports: Polymorphisms in JMJD1C are associated with pubertal onset in boys and reproductive function in men.

The testicular dysgenesis syndrome links different male reproductive disorders and can also lead to testicular cancer, which is the most common cancer among young men.

“I also wanted my PhD to investigate how small non-coding RNAs can serve as biomarkers for testicular cancer, and it was an exciting result! I showed that circulating small RNAs can function as new clinical biomarkers for testicular germ cell tumours, with the potential to outcompete existing serum tumour markers,” says Nina Mørup Nygaard about the results, which Cancers published in March 2020: Evaluation of Circulating miRNA Biomarkers of Testicular Germ Cell Tumors during Therapy and Follow-up – A Copenhagen Experience.

The most common type of testicular cancers arises from the germ cells and are called testicular germ cell tumours. They derive from a common precursor cell called germ cell neoplasia in situ (GCNIS). GCNIS is believed to be a fetal germ cell that arrested during development, escaped apoptosis and transformed into a pre-malignant cell. GCNIS can only be detected with a highly invasive procedure and is rarely diagnosed at early stages.

“With a group of colleagues, I tested a panel of microRNAs with regards to their usefulness in diagnosing testicular germ cell tumours and in monitoring patients after treatment. In accordance with previous studies, we found the microRNAs to have higher sensitivity than the currently used serum tumour markers. The microRNAs cannot diagnose GCNIS and therefore we investigated whether small RNAs present in seminal plasma could serve as diagnostic markers for GCNIS. We identified panels of small RNAs that could predict the presence of GCNIS and/or testicular germ cell tumours with high accuracy,” explains Nina Mørup Nygaard, postdoc at the Department of Growth and Reproduction, Rigshospitalet.
In May 2021 Cancers published the results: Small RNAs in Seminal Plasma as Novel Biomarkers for Germ Cell Tumors

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