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Updated: May 21, 2026
Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
Bisphenol A modulates germ cell differentiation and retinoic acid signaling in mouse ES cells
Tomohiro Aoki1, Tatsuyuki Takada
1Laboratory of Cell Engineering, Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
Abstract:
Bisphenol A (BPA) has been reported to have an adverse effect on mammalian reproduction and recognized as an endocrine disruptor. However, the molecular mechanism that causes impaired development of germ cells remains elusive. In this study, we investigated the effect of BPA using in vitro differentiation of embryonic stem (ES) cells focusing on the expression of germ cell marker genes. We found that the BPA-treated embryoid bodies (EBs), exhibited the most prominent up-regulation of meiotic entry gene Stra8 and induction mechanism appeared to be different from that of retinoic acid. Localization of aggregated Sycp3 signal in nuclei, characteristic to leptotene of meiosis, was also detected. In addition, up-regulation of ovarian markers (Foxl2 and Wnt4) and suppression of testicular markers (Sox9 and Fgf9) were observed. These results suggest that BPA might affect testicular and ovarian development as well as germ cell differentiation, and appears to induce genes responsible for ovary development.
Insights
Bisphenol A (BPA) exposure impacts embryonic stem cell differentiation, affecting germ cell development and potentially skewing gonadal development towards ovarian pathways. This endocrine disruptor influences key meiotic and sex-determining genes.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Toxicology
Background:
- Bisphenol A (BPA) is a known endocrine disruptor with adverse effects on mammalian reproduction.
- The precise molecular mechanisms underlying BPA's impact on germ cell development are not fully understood.
Purpose of the Study:
- To investigate the effects of BPA on in vitro differentiation of embryonic stem (ES) cells.
- To analyze the expression of germ cell marker genes and identify molecular pathways affected by BPA.
Main Methods:
- Utilized in vitro differentiation of mouse embryonic stem cells into embryoid bodies (EBs).
- Assessed the expression of key genes involved in germ cell development and meiosis (e.g., Stra8, Sycp3).
- Examined the expression of ovarian (Foxl2, Wnt4) and testicular (Sox9, Fgf9) marker genes.
Main Results:
- BPA-treated EBs showed significant up-regulation of the meiotic entry gene Stra8.
- Evidence of meiotic entry (Sycp3 localization) was observed in BPA-exposed cells.
- BPA exposure led to the up-regulation of ovarian markers and suppression of testicular markers, suggesting a bias towards ovarian development.
Conclusions:
- BPA exposure in vitro influences germ cell differentiation and meiosis.
- BPA appears to promote ovarian development pathways while suppressing testicular pathways.
- These findings suggest BPA can disrupt normal gonadal development and germ cell maturation.
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