Journal
REPRODUCTIVE TOXICOLOGY
Volume 34, Issue 3, Pages 463-470Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2012.06.001
Keywords
Bisphenol A; Endocrine disruptor; Germ cell; Embryonic stem cell; Stra8; Retinoic acid
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Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- Ritsumeikan Global Innovation Research Organization (R-GIRO)
- Grants-in-Aid for Scientific Research [23651248] Funding Source: KAKEN
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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. (C) 2012 Elsevier Inc. All rights reserved.
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