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Molecular Basis of Fertility Preservation and Restoration 4.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 3316

Special Issue Editor


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Guest Editor
1. The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel
2. The Center of Advanced Research and Education in Reproduction (CARER), Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel
Interests: male infertility; male fertility preservation; in vitro development of spermatogenesis; chemotherapy/irradiation and male infertility; cytokines/growth factors in the testis; acute myeloid leukemia and male infertility; rhree-dimension (3D) in vitro culture systems and spermatogenesis
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Special Issue Information

Dear Colleagues,

Fertility preservation, on both the male and female sides, is an exciting field, especially considering the urgent current need to find methods that allow parenthood with one’s own genetic background when gonadotoxic therapies risking permanent infertility are applied or when a genetic condition responsible for infertility or loss of fertility over time is present.

Numerous approaches to preserve and restore fertility are under investigation and, with the perspective of a clinical application, a better understanding of current achievements at the cellular and molecular levels is needed. Some strategies rely on the use of cryopreserved gonadal tissue or cells, such as in vitro germ cell maturation or cell and tissue transplantation, while others focus on the use of alternative sources of stem cells or on protecting in situ germ cells from gonadotoxicity. To facilitate preclinical studies, improved knowledge on molecular markers for developing germ cells could prove useful.

This Special Issue therefore focuses on current developments in the field of fertility preservation and on perspectives for fertility restoration in humans. Both original research articles and comprehensive review papers are welcomed.

Prof. Dr. Mahmoud Huleihel
Guest Editor

Manuscript Submission Information

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Keywords

  • fertility preservation
  • infertility
  • testis
  • ovary
  • spermatogonia
  • ovarian tissue
  • stem cells
  • in vitro maturation
  • metabolism
  • miRNA
  • germ cells
  • single-cell transcriptome
  • induced pluripotent stem cells
  • organ-on-chip (OoC)
  • organoids
  • microfluidic system
  • germ cell transplantation
  • epigenetics

Published Papers (2 papers)

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Research

18 pages, 5852 KiB  
Article
Effect of Granulocyte Colony-Stimulating Factor on the Development of Spermatogenesis in the Adulthood of Juvenile AML Mice Model Treated with Cytarabine
by Bara’ah Khaleel, Eitan Lunenfeld, Joseph Kapelushnik and Mahmoud Huleihel
Int. J. Mol. Sci. 2023, 24(15), 12229; https://doi.org/10.3390/ijms241512229 - 31 Jul 2023
Viewed by 989
Abstract
Pediatric acute myeloid leukemia (AML) generally occurs de novo. The treatment of AML includes cytarabine (CYT) and other medications. The granulocyte-colony stimulating factor (GCSF) is used in the clinic in cases of neutropenia after chemotherapies. We show that the administration of GCSF in [...] Read more.
Pediatric acute myeloid leukemia (AML) generally occurs de novo. The treatment of AML includes cytarabine (CYT) and other medications. The granulocyte-colony stimulating factor (GCSF) is used in the clinic in cases of neutropenia after chemotherapies. We show that the administration of GCSF in combination with CYT in AML-diagnosed mice (AML+CYT+GCSF) extended the survival of mice for additional 20 days. However, including GCSF in all treatment modalities does not affect the testis’ weight or the histology of the seminiferous tubules (STs). We show that GCSF does not affect normal ST histology from AML-, CYT-, or (AML+CYT)-treated groups compared to the relevant treated group without GCSF 2, 4, and 5 weeks post-injection. However, when comparing the percentages of normal STs between the AML+CYT+GCSF-treated groups and those without GCSF, we observe an increase of 17%–42% in STs at 4 weeks and 5.5 weeks post-injection. Additionally, we show that the injection of GCSF into the normal, AML-alone, or CYT-alone groups, or in combination with AML, significantly decreases the percentage of STs with apoptotic cells compared to the relevant groups without GCSF and to the CT (untreated mice) only 2 weeks post-injection. We also show that injection of GCSF into the CT group increases the examined spermatogonial marker PLZF within 2 weeks post-injection. However, GCSF does not affect the count of meiotic cells (CREM) but decreases the post-meiotic cells (ACROSIN) within 4 weeks post-injection. Furthermore, GCSF not only extends the survival of the AML+CYT-treated group, but it also leads to the generation of sperm (1.2 ± 0.04 × 106/mL) at 5.5 weeks post-injection. In addition, we demonstrate that the injection of GCSF into the CT group increases the RNA expression level of IL-10 but not IL-6 compared to CT 2 weeks post-treatment. However, the injection of GCSF into the AML-treated group reverses the expression levels of both IL-10 and IL-6 to normal levels compared to CT 2 weeks post-injection. Thus, we suggest that the addition of GCSF to the regimen of AML after CYT may assist in the development of future therapeutic strategies to preserve male fertility in AML prepubertal patients. Full article
(This article belongs to the Special Issue Molecular Basis of Fertility Preservation and Restoration 4.0)
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17 pages, 1850 KiB  
Article
Conserved Transcriptome Features Define Prepubertal Primate Spermatogonial Stem Cells as Adark Spermatogonia and Identify Unique Regulators
by Anukriti Singh and Brian P. Hermann
Int. J. Mol. Sci. 2023, 24(5), 4755; https://doi.org/10.3390/ijms24054755 - 1 Mar 2023
Cited by 1 | Viewed by 1910
Abstract
Antineoplastic treatments for cancer and other non-malignant disorders can result in long-term or permanent male infertility by ablating spermatogonial stem cells (SSCs). SSC transplantation using testicular tissue harvested before a sterilizing treatment is a promising approach for restoring male fertility in these cases, [...] Read more.
Antineoplastic treatments for cancer and other non-malignant disorders can result in long-term or permanent male infertility by ablating spermatogonial stem cells (SSCs). SSC transplantation using testicular tissue harvested before a sterilizing treatment is a promising approach for restoring male fertility in these cases, but a lack of exclusive biomarkers to unequivocally identify prepubertal SSCs limits their therapeutic potential. To address this, we performed single-cell RNA-seq on testis cells from immature baboons and macaques and compared these cells with published data from prepubertal human testis cells and functionally-defined mouse SSCs. While we found discrete groups of human spermatogonia, baboon and rhesus spermatogonia appeared less heterogenous. A cross-species analysis revealed cell types analogous to human SSCs in baboon and rhesus germ cells, but a comparison with mouse SSCs revealed significant differences with primate SSCs. Primate-specific SSC genes were enriched for components and regulators of the actin cytoskeleton and participate in cell-adhesion, which may explain why the culture conditions for rodent SSCs are not appropriate for primate SSCs. Furthermore, correlating the molecular definitions of human SSC, progenitor and differentiating spermatogonia with the histological definitions of Adark/Apale spermatogonia indicates that both SSCs and progenitor spermatogonia are Adark, while Apale spermatogonia appear biased towards differentiation. These results resolve the molecular identity of prepubertal human SSCs, define novel pathways that could be leveraged for advancing their selection and propagation in vitro, and confirm that the human SSC pool resides entirely within Adark spermatogonia. Full article
(This article belongs to the Special Issue Molecular Basis of Fertility Preservation and Restoration 4.0)
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