In Vitro Propagation of XXY Undifferentiated Mouse Spermatogonia: Model for Fertility Preservation in Klinefelter Syndrome Patients

Klinefelter syndrome (KS) is characterized by a masculine phenotype, supernumerary sex chromosomes (usually XXY), and spermatogonial stem cell (SSC) loss in their early life. Affecting 1 out of every 650 males born, KS is the most common genetic cause of male infertility, and new fertility preservat...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-12, Vol.23 (1), p.173
Main Authors: Galdon, Guillermo, Deebel, Nicholas A, Zarandi, Nima Pourhabibi, Pettenati, Mark J, Kogan, Stanley, Wang, Christina, Swerdloff, Ronald S, Atala, Anthony, Lue, Yanhe, Sadri-Ardekani, Hooman
Format: Article
Language:English
Subjects:
Animals
Biopsy
Cell culture
Chromosomes
Cryopreservation
Disease Models, Animal
Fertility
Fertility Preservation
Flow cytometry
Fluorescence
Fluorescence in situ hybridization
Gene expression
Hyperplasia
In vitro fertilization
Infertility
Klinefelter Syndrome
Klinefelter's syndrome
Male
male infertility
Mice
Patients
Phenotypes
Population
Preservation
Propagation
Puberty
Semen Preservation
Sex chromosomes
Somatic cells
Sperm
Spermatogonia
spermatogonia stem cells
Stem cells
Supernumerary
Testes
Testosterone
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Summary:Klinefelter syndrome (KS) is characterized by a masculine phenotype, supernumerary sex chromosomes (usually XXY), and spermatogonial stem cell (SSC) loss in their early life. Affecting 1 out of every 650 males born, KS is the most common genetic cause of male infertility, and new fertility preservation strategies are critically important for these patients. In this study, testes from 41, XXY prepubertal (3-day-old) mice were frozen-thawed. Isolated testicular cells were cultured and characterized by qPCR, digital PCR, and flow cytometry analyses. We demonstrated that SSCs survived and were able to be propagated with testicular somatic cells in culture for up to 120 days. DNA fluorescent in situ hybridization (FISH) showed the presence of XXY spermatogonia at the beginning of the culture and a variety of propagated XY, XX, and XXY spermatogonia at the end of the culture. These data provide the first evidence that an extra sex chromosome was lost during innate SSC culture, a crucial finding in treating KS patients for preserving and propagating SSCs for future sperm production, either in vitro or in vivo. This in vitro propagation system can be translated to clinical fertility preservation for KS patients.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23010173