Maternal estrogen controls retinoic acid metabolism and signaling in early vertebrate development

Fertilized eggs of lower vertebrates contain substantial amounts of steroidal hormones such as estrogen transferred from mother during oogenesis. However, molecular roles for maternal estrogen in the early embryonic development are largely unknown. Here we show that maternal estrogen and estrogen receptor-α modulate retinoic acid (RA) metabolism and RA-responsive gene expression in medaka embryos. Treatments with excess estradiol, an anti-estrogen (tamoxifen), overexpression or knockdown of estrogen receptor-α (ERα) resulted in misregulation of RA-related gene expression such as raldh2 (retinalaldehyde dehydrogenase), cyp26a1 (RA hydroxylase), fgf8 (fibroblast growth factor), rarα (RA receptor-α), and ahr1 (aryl hydrocarbon receptor). We propose that maternal estrogen/ERα plays a critical role in the feedback control of in vivo level of RA and that it also activates RA signaling for the development of hindbrain and vasculatures. This is the first report demonstrating that maternal estrogen supports successful embryonic development by controlling RA metabolism and signaling in early vertebrate embryos.Supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan