Dataset Information

Oocyte-like cells induced from mouse spermatogonial stem cells.

ABSTRACT:

Unlabelled

Background

During normal development primordial germ cells (PGCs) derived from the epiblast are the precursors of spermatogonia and oogonia. In culture, PGCs can be induced to dedifferentiate to pluripotent embryonic germ (EG) cells in the presence of various growth factors. Several recent studies have now demonstrated that spermatogonial stem cells (SSCs) can also revert back to pluripotency as embryonic stem (ES)-like cells under certain culture conditions. However, the potential dedifferentiation of SSCs into PGCs or the potential generation of oocytes from SSCs has not been demonstrated before.

Results

We report that mouse male SSCs can be converted into oocyte-like cells in culture. These SSCs-derived oocytes (SSC-Oocs) were similar in size to normal mouse mature oocytes. They expressed oocyte-specific markers and gave rise to embryos through parthenogenesis. Interestingly, the Y- and X-linked testis-specific genes in these SSC-Oocs were significantly down-regulated or turned off, while oocyte-specific X-linked genes were activated. The gene expression profile appeared to switch to that of the oocyte across the X chromosome. Furthermore, these oocyte-like cells lost paternal imprinting but acquired maternal imprinting.

Conclusions

Our data demonstrate that SSCs might maintain the potential to be reprogrammed into oocytes with corresponding epigenetic reversals. This study provides not only further evidence for the remarkable plasticity of SSCs but also a potential system for dissecting molecular and epigenetic regulations in germ cell fate determination and imprinting establishment during gametogenesis.

SUBMITTER: Wang L

PROVIDER: S-EPMC3505744 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Publications

Oocyte-like cells induced from mouse spermatogonial stem cells.

Wang Lu L Cao Jinping J Ji Ping P Zhang Di D Ma Lianghong L Dym Martin M Yu Zhuo Z Feng Lixin L

Cell & bioscience 20120806 1

<h4>Unlabelled</h4><h4>Background</h4>During normal development primordial germ cells (PGCs) derived from the epiblast are the precursors of spermatogonia and oogonia. In culture, PGCs can be induced to dedifferentiate to pluripotent embryonic germ (EG) cells in the presence of various growth factors. Several recent studies have now demonstrated that spermatogonial stem cells (SSCs) can also revert back to pluripotency as embryonic stem (ES)-like cells under certain culture conditions. However, ...[more]

PMID: 22863141

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Project description:Graphical abstract Highlights • Background: The risk of infertility after chemotherapy is unpredictable in children with cancer.• Our in vitro study demonstrated short-term damage of chemotherapy on immature mouse testis.• Cisplatin and doxorubicin induce acute spermatogonial stem cell loss that does not persist two months later.• High concentrations of cisplatin impair later phases of spermatogenesis in the long-term. Chemotherapy can affect testis development of young boys with cancer, reducing the chances of fatherhood in adulthood. Studies using experimental models are needed to determine the damage caused by individual chemotherapy drugs in order to predict the risk of infertility and direct patients towards appropriate fertility preservation options. Here, we investigated the individual role of two drugs, cisplatin and doxorubicin, using an in vitro culture model of prepubertal (postnatal day 5) mouse testis that supports induction and maintenance of full spermatogenesis. Twenty-four hour exposure with either drug at clinically-relevant doses (0.25, 0.5 or 0.75 ?g/mL for cisplatin, or 0.01, 0.03 or 0.05 ?g/mL for doxorubicin), induced an acute significant loss of spermatogonial stem cells (SSCs; PLZF+), proliferating SSCs (PLZF+BrdU+), total germ cells (MVH+), and spermatocytes (SCP3+) one week after chemotherapy exposure. By the time of the first (Week 4) and second (Week 8) waves of spermatogenesis, there was no longer any effect on SSC or proliferating SSC numbers in drug-exposed testis compared to untreated tissue: however, the populations of total germ cells and spermatocytes were still lower in the higher-dose cisplatin treated groups, along with a reduced frequency of round and elongated spermatids in both cisplatin- and doxorubicin-treated testis fragments. Overall, this study details a direct impairment of germ cell development following acute chemotherapy-induced damage during the prepubertal phase, most likely due to an effect on SSCs, using an in vitro culture system that successfully recapitulates key events of mouse spermatogenesis.

Dataset Information

Oocyte-like cells induced from mouse spermatogonial stem cells.

Unlabelled

Background

Results

Conclusions

Publications

Oocyte-like cells induced from mouse spermatogonial stem cells.

Similar Datasets

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