Graduate School of Nanobioscience, Yokohama City University, Yokohama 236-0027, Japan; Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.
Graduate School of Nanobioscience, Yokohama City University, Yokohama 236-0027, Japan.
Reprod Toxicol. 2019 Jun;86:56-61. doi: 10.1016/j.reprotox.2019.03.006. Epub 2019 Mar 30.
In female mice, the Müllerian duct develops into the oviduct, uterus and vagina. The fate of epithelia is determined by factors secreted from the mesenchyme. Retinoic acid (RA) and its receptors are present in the mesenchyme of cranial Müllerian duct. RA induces Müllerian duct to uterine epithelial differentiation whereas inhibition of RA receptors induces vaginal epithelial differentiation. Thus, RA signaling in the Müllerian duct is required to promote differentiation of the mesenchyme into the future uterus. Perinatal estrogen exposure induces various abnormalities in Müllerian duct-derived organs. These include a cranial shift of the border among oviduct, uterus and vagina as well as precancerous lesions suppressed by co-treatment with RA and estrogen. Since RA synthesis enzymes and receptors are expressed both in the epithelium and stroma after birth, RA signaling may act in the epithelia to maintain adult epithelial homeostasis and to prevent irreversible lesions induced by perinatal estrogen exposure.
在雌性小鼠中，缪勒管发育为输卵管、子宫和阴道。上皮的命运由间质分泌的因子决定。视黄酸（RA）及其受体存在于颅缪勒管的间质中。RA 诱导缪勒管向子宫上皮分化，而 RA 受体的抑制诱导阴道上皮分化。因此，RA 信号在缪勒管中是促进间质分化为未来子宫所必需的。围产期雌激素暴露会引起缪勒管衍生器官的各种异常。这些异常包括输卵管、子宫和阴道之间的边界向颅侧移位，以及通过与 RA 和雌激素联合治疗抑制的癌前病变。由于 RA 合成酶和受体在出生后均在上皮和基质中表达，因此 RA 信号可能在上皮中发挥作用，以维持成年上皮的稳态，并防止围产期雌激素暴露引起的不可逆损伤。
