Critical role of V1a vasopressin receptor in murine parturition

Critical role of V1a vasopressin receptor in murine parturition
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V1a 加压素受体在小鼠分娩中的关键作用

DOI:
10.1093/biolre/ioz220
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发表时间:
2020
影响因子:
3.6
通讯作者:
Taka-aki Koshimizu
Taka-aki Koshimizu
中科院分区:
生物学2区
文献类型:
--
作者:
Hiroyoshi Tsuchiya; Shyota Fujimura; Yoko Fujiwara; Taka-aki Koshimizu

文献摘要

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生殖生理过程的精确机制,如分娩开始,目前还知之甚少。催产素(OT)是一种广为人知的子宫强直症,临床上被用作促进分娩的药物。加压素(VP)是一种类似于催产素的垂体后叶激素,也被认为与生殖生理有关。在这项研究中,我们发现与野生型小鼠相比,小鼠中V1a受体亚型(V1aR)的完全缺乏会导致仔鼠数量减少、分娩延迟和产后出血增加。在VP受体亚型中,只有V1aR在小鼠子宫中表达,其分布模式与催产素受体(Otr)不同,V1aR主要分布在环状肌层,而OtR在环状和纵状肌层均有较强的表达。在Avpr1a基因缺陷小鼠的妊娠子宫中,VP或OT引起的环状肌层最大收缩力减弱。相反,在Avpr1a缺乏的子宫中,虽然OT的表达减少,但OTR的表达显著增加。这些结果表明,V1aR缺乏不仅降低了子宫收缩力量,而且还扰乱了与生殖生理有关的基因的表达。因此,V1aR对于最大限度地收缩环形肌层来分娩幼崽是必要的。本研究揭示了V1aR在小鼠生理收缩和足月分娩中的重要作用。
The precise mechanisms of the reproductive physiological processes, such as labor initiation, are poorly understood. Oxytocin (OT) is one of the well-known uterotonics and is clinically adopted as a medication to facilitate childbirth. Vasopressin (VP), a posterior pituitary hormone similar to OT, has also been proposed to be involved in the reproductive physiology. In this study, we found that a total deficiency of V1a receptor subtype (V1aR) in mice resulted in a reduced number of pups, delayed labor initiation, and increased post-delivery hemorrhage compared with those in wild-type mice. Among the VP receptor subtypes, only V1aR was found to be expressed in the murine uterus, and its distribution pattern was different from that of the oxytocin receptor (OTR); V1aR expression was mainly distributed in the circular myometrium, whereas OTR was strongly expressed in both the circular and longitudinal myometrium. The maximum contractile force of the circular myometrium, induced by VP or OT, was attenuated in the pregnant uterus ofAvpr1a-deficient mice. Contrarily, while OT expression was decreased in theAvpr1a-deficient uterus, OTR expression was significantly increased. These results suggest that V1aR deficiency not only reduces the uterine contractile force but also perturbs the expression of genes responsible for the reproductive physiology. Therefore, V1aR is necessary to exert the maximum contraction of the circular myometrium to deliver pups. This study revealed an important role of V1aR in physiological contraction and term parturition in mice.