Bisphenol A modulates germ cell differentiation and retinoic acid signaling in mouse ES cells.
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.
Laboratory of Cell Engineering, Department of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
Tomohiro
T
Aoki
Tatsuyuki
T
Takada
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000633:toxicity*; D011506:Proteins / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000378:metabolism*; D000098826:Bisphenol A Compounds
D048868:Adaptor Proteins, Signal Transducing; D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011506:Proteins; D014212:Tretinoin; C102019:Stra8 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds