TRPV4 is involved in levonorgestrel-induced reduction in oviduct ciliary beating
TRPV4 is involved in levonorgestrel-induced reduction in oviduct ciliary beating
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TRPV4 参与左炔诺孕酮诱导的输卵管纤毛跳动减少
DOI：
10.1002/path.5233
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发表时间：
2019-05-01
影响因子：
7.3
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Li, Cheng;Wu, Yan-Ting;Zhang, Jian
以往的研究表明，左炔诺孕酮（LNG）诱导的紧急避孕失败后，输卵管妊娠的风险增加，这是由于睫状体运动减少响应LNG。然而，了解的机制，液化天然气诱导的纤毛搏动频率（CBF）的减少是有限的。瞬时受体电位香草酸（TRPV）4通道广泛分布于女性生殖道，在正常生理条件下激活后产生Ca 2+内流，调节CBF。本研究旨在探讨LNG是否通过调节TRPV 4通道减少输卵管CBF，导致胚胎滞留在输卵管中并随后发生输卵管妊娠。本研究为TRPV 4在输卵管妊娠患者输卵管组织中的表达下调提供了证据，并与血清孕酮水平呈负相关。LNG下调TRPV 4的表达，限制钙内流，降低小鼠输卵管CBF。此外，纤毛细胞的分布和纤毛的形态没有改变后，LNG的管理。孕酮受体拮抗剂RU 486或TRPV 4激动剂4 α-佛波醇12，13-二癸酸酯（4 α-PDD）可部分逆转LNG诱导的输卵管和小鼠输卵管中CBF和胚胎滞留的减少。结果提示LNG可通过下调TRPV 4的表达，降低人和小鼠的CBF，提示LNG可能是输卵管妊娠的机制之一。(c)2019作者病理学杂志由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版。
Previous studies revealed the increasing risk of tubal pregnancy following failure of levonorgestrel (LNG)-induced emergency contraception, which was attributed to the reduced ciliary motility in response to LNG. However, understanding of the mechanism of LNG-induced reduction in the ciliary beat frequency (CBF) is limited. The transient receptor potential vanilloid (TRPV) 4 channel is located widely in the female reproductive tract and generates an influx of Ca2+ following its activation under normal physiological conditions, which regulates the CBF. The present study aimed to explore whether LNG reduced the CBF in the Fallopian tubes by modulating TRPV4 channels, leading to embryo retention in the Fallopian tubes and subsequent tubal pregnancy. The study provided evidence that the expression of TRPV4 was downregulated in the Fallopian tubes among patients with tubal pregnancy and negatively correlated with the serum level of progesterone. LNG downregulated the expression of TRPV4, limiting the calcium influx to reduce the CBF in mouse oviducts. Furthermore, the distribution of ciliated cells and the morphology of cilia did not change following the administration of LNG. LNG-induced reduction in the CBF and embryo retention in the Fallopian tubes and in mouse oviducts were partially reversed by the progesterone receptor antagonist RU486 or the TRPV4 agonist 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD). The results indicated that LNG could downregulate the expression of TRPV4 to reduce the CBF in both humans and mice, suggesting the possible mechanism of tubal pregnancy. (c) 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.