ArticleJournal of ovarian research2018
Retinoic acid enhances germ cell differentiation of mouse skin-derived stem cells.
Article in Journal of ovarian research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Ascorbic acid enhancesFrontiers in cell and developmental biology · 2026Article
- mTORC1 regulates the proliferation of SOX9Histochemistry and cell biology · 2025Article
- Advances in Molecular Biology and Immunology of Spermatozoa and Fertilization in Domestic Animals: Implications for Infertility and Assisted Reproduction.Current molecular medicine · 2025Review
- The retinoic acid response is a minor component of the cardiac phenotype in H9c2 myoblast differentiation.BMC genomics · 2023Article
- Differentiation of human endometrial stem cells encapsulated in alginate hydrogel into oocyte-like cells.BioImpacts : BI · 2023Article
- AOP Key Event Relationship report: Linking decreased retinoic acid levels with disrupted meiosis in developing oocytes.Current research in toxicology · 2022Article
- Primordial germ cells can be differentiated by retinoic acid and progesterone induction from embryonic stem cells.Journal of biosciences · 2021Article
- In Vitro Generation of Oocyte Like Cells and Their In Vivo Efficacy: How Far We have been Succeeded.Cells · 2020Review
- The Usefulness of Retinoic Acid Supplementation during In Vitro Oocyte Maturation for the In Vitro Embryo Production of Livestock: A Review.Animals : an open access journal from MDPI · 2019Review
- Generation of male germ cellsAsian journal of andrologyReview
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRetinoic acid (RA) signaling has been identified as a key driver in male and female gamete development. The presence of RA is a critical step in the initiation of meiosis and is required for the production of competent oocytes from primordial germ cells. Meiosis has been identified as a difficult biological process to recapitulate in vitro, when differentiating stem cells to germ cells. We have previously shown that primordial germ cell-like cells, and more advanced oocyte-like cells (OLCs), can be formed by differentiating mouse skin-derived stem cells. However, the OLCs remain unable to function due to what appears to be failure of meiotic initiation. The aim of this study was to determine the effect of RA treatment, during stem cell differentiation to germ cells, particularly on the initiation of meiosis.
resultsUsing qPCR we found significant increases in the meiosis markers Stra8 and Sycp3 and a significant reduction in the meiosis inhibitor Nanos2, in the differentiating populations. Furthermore, OLCs from the RA treated group, expressed significantly more of the meiosis regulatory gene Marf1 and the oocyte marker Oct4. At the protein level RA treatment was found to increase the expression of the gap junction protein CX43 and the pluripotency marker OCT4. Moreover, the expression of SYCP3 was significantly upregulated and the localization pattern better matched that of control fetal ovarian cells. RA treatment also improved the structural integrity of the OLCs produced by initiating the expression of all three zona pellucida transcripts (Zp1-3) and improving ZP3 expression levels and localization. Finally, the addition of RA during differentiation led to an almost two-fold increase in the number of OLCs recovered and increased their in vitro growth.
conclusionRA is a key driver in the formation of functioning gametes and its addition during stem cell to germ cell differentiation improves OLCs entry into meiosis.
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