Li Shuai, O'Neill Sofia R S, Zhang Yong, Holtzman Michael J, Takemaru Ken-Ichi, Korach Kenneth S, Winuthayanon Wipawee
School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
FASEB J. 2017 Apr;31(4):1595-1607. doi: 10.1096/fj.201601128R. Epub 2017 Jan 12.
Newly fertilized embryos spend the first few days within the oviduct and are transported to the uterus, where they implant onto the uterine wall. An implantation of the embryo before reaching the uterus could result in ectopic pregnancy and lead to maternal death. Estrogen is necessary for embryo transport in mammals; however, the mechanism involved in estrogen-mediated cellular function within the oviduct remains unclear. In this study, we show in mouse models that ciliary length and beat frequency of the oviductal epithelial cells are regulated through estrogen receptor α (ESR1) but not estrogen receptor β (ESR2). Gene profiling indicated that transcripts in the WNT/β-catenin (WNT/CTNNB1) signaling pathway were regulated by estrogen in mouse oviduct, and inhibition of this pathway in a whole oviduct culture system resulted in a decreased embryo transport distance. However, selective ablation of CTNNB1 from the oviductal ciliated cells did not affect embryo transport, possibly because of a compensatory mechanism intact CTNNB1 in the adjacent secretory cells. In summary, we demonstrated that disruption of estrogen signaling in oviductal epithelial cells alters ciliary function and impairs embryo transport. Therefore, our findings may provide a better understanding of etiology of the ectopic pregnancy that is associated with alteration of estrogen signals.-Li, S., O'Neill, S. R. S., Zhang, Y., Holtzman, M. J., Takemaru, K.-I., Korach, K. S., Winuthayanon, W. Estrogen receptor α is required for oviductal transport of embryos.
新受精的胚胎在输卵管内度过最初几天，然后被输送到子宫，在那里它们植入子宫壁。胚胎在到达子宫之前植入可能会导致异位妊娠并导致母体死亡。雌激素对哺乳动物的胚胎运输是必需的；然而，雌激素介导的输卵管内细胞功能所涉及的机制仍不清楚。在这项研究中，我们在小鼠模型中表明，输卵管上皮细胞的纤毛长度和摆动频率是通过雌激素受体α（ESR1）而不是雌激素受体β（ESR2）来调节的。基因分析表明，WNT/β-连环蛋白（WNT/CTNNB1）信号通路中的转录本在小鼠输卵管中受雌激素调节，在全输卵管培养系统中抑制该通路会导致胚胎运输距离缩短。然而，从输卵管纤毛细胞中选择性切除CTNNB1并不影响胚胎运输，这可能是因为相邻分泌细胞中完整的CTNNB1存在补偿机制。总之，我们证明了输卵管上皮细胞中雌激素信号的破坏会改变纤毛功能并损害胚胎运输。因此，我们的发现可能有助于更好地理解与雌激素信号改变相关的异位妊娠的病因。-李，S.，奥尼尔，S.R.S.，张，Y.，霍尔兹曼，M.J.，武丸，K.-I.，科拉奇，K.S.，维努萨亚农，W.胚胎输卵管运输需要雌激素受体α 。
