Retinoic acid regulates germ cell differentiation in mouse embryonic stem cells through a Smad-dependent pathway

Chen, Wen; Jia, Wenwen; Wang, Kai; Zhou, Qian; Leng, Ye; Duan, Tony; Kang, Jiuhong

doi:10.1016/j.bbrc.2012.01.078

Cited by 41 publications

(36 citation statements)

References 26 publications

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“…As mentioned already, germ cells respond by up-regulating Stra8 in the presence of very low levels of RA in vitro (as little as 1nM; (Bowles et al, 2010;Chen et al, 2012;Ohta et al, 2010;Zhou et al, 2008)). Additionally, redundancy within the RALDH family has been reported in tissues such as the dorsal retina (Fan et al, 2003) and it is possible that RALDH1 expressed in the ovary produces sufficient levels of RA in the absence of RALDH2 and RALDH3 to induce meiosis even if not sufficiently high to elicit RARE-LacZ reporter expression.…”

Section: Challenging the Retinoic Acid Theorymentioning

confidence: 65%

“…While exogenous RA was initially implicated in germ cell meiosis in organ culture using much higher concentrations (0.7-1mM; (Bowles et al, 2006;Koubova et al, 2006), more recent studies have demonstrated that much lower levels (as low as 1nM) are sufficient for not only activation of Stra8 but also functional meiosis (Bowles et al, 2010;Chen et al, 2012;Ohta et al, 2010;Zhou et al, 2008). Further, in vitro, high levels of RA are detrimental to germ cell survival in both testes and ovaries (Best and Adams 2009).…”

Section: How Much Retinoic Acid?mentioning

confidence: 99%

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Regulation of germ cell meiosis in the fetal ovary

Spiller¹,

Bowles²,

Koopman³

2012

Int. J. Dev. Biol.

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Fertility depends on correct regulation of meiosis, the special form of cell division that gives rise to haploid gametes. In female mammals, germ cells enter meiosis during fetal ovarian development, while germ cells in males avoid entering meiosis until puberty. Decades of research have shown that meiotic entry, and germ cell sex determination, are not initiated intrinsically within the germ cells. Instead, meiosis is induced by signals produced by the surrounding somatic cells. More recently, retinoic acid (RA), the active derivative of vitamin A, has been implicated in meiotic induction during fetal XX and postnatal XY germ cell development. Evidence for an intricate system of RA synthesis and degradation in the fetal ovary and testis has emerged, explaining past observations of infertility in vitamin A-deficient rodents. Here we review how meiosis is triggered in fetal ovarian germ cells, paying special attention to the role of RA in this process.

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Section: Challenging the Retinoic Acid Theorymentioning

confidence: 65%

Section: How Much Retinoic Acid?mentioning

confidence: 99%

Regulation of germ cell meiosis in the fetal ovary

Spiller¹,

Bowles²,

Koopman³

2012

Int. J. Dev. Biol.

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“…Glial cell line-derived neurotrophic factor (GDNF) is required for SSC maintenance and proliferation39. RA stimulates PGC division and contributes to meiosis through the CYP26/STRA8 signal pathways74041. Testosterone secreted by Leydig cells is necessary for spermatogenesis, and it also acts on Sertoli cells to promote male germ cell differentiation42.…”

Section: Discussionmentioning

confidence: 99%

Induction of Germ Cell-like Cells from Porcine Induced Pluripotent Stem Cells

Wang

Xiang

Zhang

et al. 2016

Sci Rep

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The ability to generate germ cells from pluripotent stem cells (PSCs) is valuable for human regenerative medicine and animal breeding. Germ cell-like cells (GCLCs) have been differentiated from mouse and human PSCs, but not from porcine PSCs, which are considered an ideal model for stem cell applications. Here, we developed a defined culture system for the induction of primordial germ cell-like cells (PGCLCs) from porcine induced PSCs (piPSCs). The identity of the PGCLCs was characterized by observing cell morphology, detecting germ cell marker gene expression and evaluating epigenetic properties. PGCLCs could further differentiate into spermatogonial stem cell-like cells (SSCLCs) in vitro. Importantly, meiosis occurred during SSCLC induction. Xenotransplantation of GCLCs into seminiferous tubules of infertile immunodeficient mice resulted in immunohistochemically identifiable germ cells in vivo. Overall, our study provides a feasible strategy for directing piPSCs to the germ cell fate and lays a foundation for exploring germ cell development mechanisms.

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“…In spite of that, oocyte-like cells did not express some important oocyte-specific genes, such as VASA, DAZL , and FIGLA , and therefore exhibited the characteristics of pluripotent stem cells more than of competent oocytes. As shown in the model of human and mouse ESCs, the expression of germ cell-specific genes (including VASA ) in oocyte-like cells developed in vitro can be regulated by different culture conditions [7, 10], for example, by the addition of retinoic acid into the culture medium that regulates germ cell differentiation through a Smad-dependent pathway [44]; therefore the possibilities of in vitro “oogenesis” in this study were far from being exhausted. As previously proposed, oocyte-like cells developed in vitro could also be matured in vivo by transplantation into other organs, tissues, or ovarian biopsies [5, 23]; it may be possible to autotransplant the oocyte-like cells to in vivo direct their growth, maturity, and function or perhaps to “awaken” the ovaries in women with severe ovarian infertility, if sure that teratoma would not form.…”

Section: Discussionmentioning

confidence: 99%

Expression of Pluripotency and Oocyte-Related Genes in Single Putative Stem Cells from Human Adult Ovarian Surface Epithelium CulturedIn Vitroin the Presence of Follicular Fluid

Virant‐Klun

Skutella²,

Kubista³

et al. 2013

BioMed Research International

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The aim of this study was to trigger the expression of genes related to oocytes in putative ovarian stem cells scraped from the ovarian surface epithelium of women with premature ovarian failure and cultured in vitro in the presence of follicular fluid, rich in substances for oocyte growth and maturation. Ovarian surface epithelium was scraped and cell cultures were set up by scrapings in five women with nonfunctional ovaries and with no naturally present mature follicles or oocytes. In the presence of donated follicular fluid putative stem cells grew and developed into primitive oocyte-like cells. A detailed single-cell gene expression profiling was performed to elucidate their genetic status in comparison to human embryonic stem cells, oocytes, and somatic fibroblasts. The ovarian cell cultures depleted/converted reproductive hormones from the culture medium. Estradiol alone or together with other substances may be involved in development of these primitive oocyte-like cells. The majority of primitive oocyte-like cells was mononuclear and expressed several genes related to pluripotency and oocytes, including genes related to meiosis, although they did not express some important oocyte-specific genes. Our work reveals the presence of putative stem cells in the ovarian surface epithelium of women with premature ovarian failure.

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Retinoic acid regulates germ cell differentiation in mouse embryonic stem cells through a Smad-dependent pathway

Cited by 41 publications

References 26 publications

Regulation of germ cell meiosis in the fetal ovary

Regulation of germ cell meiosis in the fetal ovary

Induction of Germ Cell-like Cells from Porcine Induced Pluripotent Stem Cells

Expression of Pluripotency and Oocyte-Related Genes in Single Putative Stem Cells from Human Adult Ovarian Surface Epithelium CulturedIn Vitroin the Presence of Follicular Fluid

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