文章基本信息

标题：Retinoic acid signaling determines the fate of uterine stroma in the mouse Müllerian duct
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作者：Tadaaki Nakajima ; Taisen Iguchi ; Tomomi Sato 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：50
页码：14354-14359
DOI：10.1073/pnas.1608808113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceOviduct, uterus, and vagina are all derived from the Mullerian duct. Epithelial fate of these female reproductive organs in developing mice is determined by factors secreted from the stroma; however, how the preceding stromal differentiation of female reproductive tracts from the Mullerian duct occurs is still unclear. This study showed that retinoic acid (RA) signaling was activated in the proximal Mullerian duct, which develops into oviduct and uterus. Furthermore, RA treatment induced uterine stromal differentiation, whereas inhibition of RA receptor signaling induced vaginal stromal differentiation. Therefore, we concluded that RA establishes a border between the stroma of uterus and vagina. The Mullerian duct develops into the oviduct, uterus, and vagina, all of which are quite distinct in their morphology and function. The epithelial fate of these female reproductive organs in developing mice is determined by factors secreted from the stroma; however, how stromal differentiation occurs in the female reproductive organs derived from the Mullerian duct is still unclear. In the present study, roles of retinoic acid (RA) signaling in developing female reproductive tracts were investigated. Retinol dehydrogenase 10 (RDH10) and aldehyde dehydrogenase family 1 subfamily A2 (ALDH1A2) mRNAs and proteins and transactivation activity of endogenous RA were found in the stroma of proximal Mullerian ducts and gradually decreased from the proximal to caudal regions in fetal mice. In organ-cultured Mullerian ducts, retinaldehyde or RA treatment induced uterine epithelial differentiation, defined as a layer of columnar epithelial cells negative for oviductal and vaginal epithelial markers. In contrast, inhibition of RA receptor (RAR) signaling induced vaginal epithelial differentiation, characterized as vaginal epithelial marker genes-positive stratified epithelium. Grafting experiments of the organ-cultured Mullerian duct revealed irreversible epithelial fate determination. Although RAR did not directly bind to the homeobox A10 (Hoxa10) promoter region, RA-RAR signaling stimulated Hoxa10 expression. Thus, RA-RAR signaling in the Mullerian duct determines the fate of stroma to form the future uterus and vagina.
关键词：Müllerian duct ; oviduct ; uterus ; vagina ; retinoic acid