Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct;44(10):2273-2284.
doi: 10.1007/s40618-021-01534-3. Epub 2021 Mar 4.

PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile

F Faja  1 , F Finocchi  1   2 , T Carlini  1 , F Rizzo  1 , F Pallotti  1 , M Spaziani  3 , G Balercia  2 , A Lenzi  1 , D Paoli  4 , F Lombardo  1
Affiliations

PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile

F Faja et al. J Endocrinol Invest. 2021 Oct.

Abstract

Purpose: Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11A polymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases.

Methods: Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11A polymorphisms using peripheral blood samples.

Results: Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11A sequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number.

Conclusions: Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer.

Keywords: Hormones; PDE11A; Polymorphisms; Spermatogenesis; Testicular germ cell tumours; cAMP signaling.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Distribution of SNP G223A and A288G in the two study groups: a distribution of SNP G223A between cases and controls, b distribution of SNP A288G between cases and controls
Fig. 2
Fig. 2
Association between total sperm number and the examined SNPs after correction for FSH values: a estimated marginal means ± standard errors of total sperm number (106/ejaculate) for genotype G223A, b estimated marginal means ± standard errors of total sperm number (106/ejaculate) for genotype A288G
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bosetti C, Bertuccio P, Chatenoud L, Negri E, La Vecchia C, Levi F. Trends in mortality from urologic cancers in Europe, 1970–2008. Eur Urol. 2011;60(1):1–15. doi: 10.1016/j.eururo.2011.03.047. - DOI - PubMed
    1. Fukawa T, Kanayama HO. Current knowledge of risk factors for testicular germ cell tumors. Int J Urol. 2018;25(4):337–344. doi: 10.1111/iju.13519. - DOI - PubMed
    1. Messerschmidt DM, Knowles BB, Solter D. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev. 2014;28(8):812–828. doi: 10.1101/gad.234294.113. - DOI - PMC - PubMed
    1. Murray MJ, Nicholson JC, Coleman N. Biology of childhood germ cell tumours, focussing on the significance of microRNAs. Andrology. 2015;3(1):129–139. doi: 10.1111/andr.277. - DOI - PMC - PubMed
    1. Murray MJ, Huddart RA, Coleman N. The present and future of serum diagnostic tests for testicular germ cell tumours. Nat Rev Urol. 2016;13(12):715–725. doi: 10.1038/nrurol.2016.170. - DOI - PubMed

MeSH terms

Supplementary concepts

LinkOut - more resources