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Development and Disease-Dependent Dynamics of Spermatogonial Subpopulations in Human Testicular Tissues

Joana M D Portela1,2, Laura Heckmann1, Joachim Wistuba1

  • 1Center of Reproductive Medicine and Andrology, Institute of Reproductive and Regenerative Biology, Albert-Schweitzer-Campus 1, Building D11, 48149 Münster, Germany.

Journal of Clinical Medicine
|January 18, 2020
PubMed

Insights

Cancer treatments and diseases can impact male fertility by altering spermatogonia. This study found reduced spermatogonial density in patients, with impaired DNA methylation in sickle cell disease patients, impacting fertility preservation.

Area of Science:

  • Reproductive biology
  • Male infertility research
  • Spermatogonial stem cell biology

Background:

  • Cancer therapies and non-malignant disease treatments can impair spermatogonial function, leading to male infertility.
  • Limited data exists on molecular properties of spermatogonia and disease/treatment effects on subpopulations.
  • Fertility preservation programs store tissues, necessitating understanding of spermatogonial changes.

Purpose of the Study:

  • To assess changes in spermatogonial subpopulation density and percentage during development and in disease/treatment contexts.
  • To investigate the influence of disease and/or treatment on spermatogonial markers (MAGEA4, UTF1, PCNA) and DNA methylation (5mC).
  • To evaluate the implications for fertility preservation strategies.

Main Methods:

  • Analysis of testicular tissues from prepubertal development (n=13) and disease/treatment cohorts (n=18) from fertility preservation programs.
  • Utilized markers for spermatogonia (MAGEA4), undifferentiated spermatogonia (UTF1), proliferation (PCNA), and global DNA methylation (5mC).
  • Quantified density and percentage of spermatogonial subpopulations and correlated with age, disease, and treatment.

Main Results:

  • During normal development, only the density of 5mC-positive spermatogonia increased with age.
  • Patients with disease/treatment showed reduced density of UTF1-, PCNA-, and 5mC-positive spermatogonia; percentages remained stable.
  • Sickle cell disease patients on hydroxyurea had reduced density and percentage of 5mC-positive spermatogonia, indicating impaired DNA methylation establishment.

Conclusions:

  • Generally, reduced spermatogonial density does not affect undifferentiated/proliferating cell percentages or global methylation establishment.
  • Impaired spermatogonial DNA methylation establishment in sickle cell disease patients is a critical finding.
  • These molecular changes have significant implications for the efficacy of fertility preservation for affected individuals.
Keywords:
5mCMAGEA4PCNAUTF1fertility preservationhuman male infertilityimmature testissickle cell diseasespermatogonia

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