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Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?

التفاصيل البيبلوغرافية
العنوان: Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?
المؤلفون: Van Saen D, Elissavet Ntemou, Prashant Kadam, Jaime Onofre, Ellen Goossens
المساهمون: Basic (bio-) Medical Sciences, Biology of the Testis
المصدر: Stem Cell Research & Therapy
Stem Cell Research & Therapy, Vol 10, Iss 1, Pp 1-10 (2019)
بيانات النشر: Springer Science and Business Media LLC, 2019.
سنة النشر: 2019
مصطلحات موضوعية: Male, 0301 basic medicine, Litter (animal), Infertility, Offspring, Medicine (miscellaneous), Spermatogonial stem cells, Biology, Mesenchymal Stem Cell Transplantation, Biochemistry, Genetics and Molecular Biology (miscellaneous), DNA Methyltransferase 3A, Epigenesis, Genetic, Male infertility, lcsh:Biochemistry, Histones, Andrology, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, lcsh:QD415-436, DNA (Cytosine-5-)-Methyltransferases, Fertility restoration, Co transplantation, lcsh:R5-920, Transplantation, 030219 obstetrics & reproductive medicine, Research, Lysine, Reproduction, Mesenchymal stem cell, Acetylation, Cell Biology, Transforming growth factor beta, medicine.disease, Spermatogonia, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Reproductive efficiency, biology.protein, Mesenchymal stem cells, Molecular Medicine, Epigenetics, Stem cell, lcsh:Medicine (General)
الوصف: BackgroundSpermatogonial stem cell transplantation (SSCT) is a promising therapy in restoring the fertility of childhood cancer survivors. However, the low efficiency of SSCT is a significant concern. SSCT could be improved by co-transplanting transforming growth factor beta 1 (TGFβ1)-induced mesenchymal stem cells (MSCs). In this study, we investigated the reproductive efficiency and safety of co-transplanting spermatogonial stem cells (SSCs) and TGFβ1-induced MSCs.MethodsA mouse model for long-term infertility was used to transplant SSCs (SSCT,n = 10) and a combination of SSCs and TGFβ1-treated MSCs (MSi-SSCT,n = 10). Both transplanted groups and a fertile control group (n = 7) were allowed to mate naturally to check the reproductive efficiency after transplantation. Furthermore, the testes from transplanted males and donor-derived male offspring were analyzed for the epigenetic markers DNA methyltransferase 3A (DNMT3A) and histone 4 lysine 5 acetylation (H4K5ac).ResultsThe overall tubular fertility index (TFI) after SSCT (76 ± 12) was similar to that after MSi-SSCT (73 ± 14). However, the donor-derived TFI after MSi-SSCT (26 ± 14) was higher compared to the one after SSCT (9 ± 5;P = 0.002), even after injecting half of the number of SSCs in MSi-SSCT. The litter sizes after SSCT (3.7 ± 3.7) and MSi-SSCT (3.7 ± 3.6) were similar but differed significantly with the control group (7.6 ± 1.0;P +offspring per litter obtained after SSCT (1.6 ± 0.5) and MSi-SSCT (2.0 ± 1.0) was also similar. The expression of DNMT3A and H4K5ac in germ cells of transplanted males was found to be significantly reduced compared to the control group. However, in donor-derived offspring, DNMT3A and H4K5ac followed the normal pattern.ConclusionCo-transplanting SSCs and TGFβ1-treated MSCs results in reproductive efficiency as good as SSCT, even after transplanting half the number of SSCs. Although transplanted males showed lower expression of DNMT3A and H4K5ac in donor-derived germ cells, the expression was restored to normal levels in germ cells of donor-derived offspring. This procedure could become an efficient method to restore fertility in a clinical setup, but more studies are needed to ensure safety in the long term.
تدمد: 1757-6512
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b7ce07f216506043f0129bc6aca3fee3
https://doi.org/10.1186/s13287-019-1420-9
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....b7ce07f216506043f0129bc6aca3fee3
قاعدة البيانات: OpenAIRE
الوصف
تدمد:17576512