Opposing actions of prostaglandins and oxytocin determine the onset of murine labor
Opposing actions of prostaglandins and oxytocin determine the onset of murine labor
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DOI：
10.1073/pnas.95.20.11875
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发表时间：
1998-09-29
影响因子：
11.1
通讯作者：
Muglia, LJ
中科院分区：
文献类型：
--
作者：
Gross, GA;Imamura, T;Muglia, LJ
前列腺素（pg）最近被证明对小鼠分娩至关重要。为了剖析两种环加氧酶（COX）异构体对妊娠期PGs合成的贡献，我们对COX-l缺陷小鼠的分娩表型进行了表征。我们发现有针对性地破坏COX-1基因的小鼠延迟分娩导致新生儿死亡。COX-1缺失的雌性与COX-1完整的雄性交配，以及COX-1缺失或完整胚胎的囊胚移植到野生型养母体内的结果，证明了母体COX-1对于正常分娩的必要性和充分性。COX-1在妊娠小鼠子宫内通过原位杂交诱导表达；这种诱导作用局限于蜕膜。子宫PGs的测量进一步证实COX-1占PGF2 α产生的大部分。为了评估PGs与催产素在小鼠分娩过程中的相互作用，我们制造了催产素和cox - 1缺乏症小鼠，令人惊讶的是，催产素和cox - 1缺乏症小鼠在正常时间开始分娩。COX-1缺失小鼠的黄体溶解能力受损，表现为妊娠后期血清黄体酮浓度和卵巢组织学升高，子宫催产素受体诱导延迟。相反，催产素和COX-1同时缺乏，在PGF2 α分泌不升高的情况下，通过允许黄体溶解恢复正常分娩。这些发现表明COX-1对小鼠正常分娩至关重要。一个关键的功能是克服妊娠后期催产素的黄体促生作用。
Prostaglandins (PGs) have been recently proven essential for parturition in mice. To dissect the contributions of the two cyclooxygenase (COX) isoforms to the synthesis of PGs during pregnancy, we have characterized the parturition phenotype of COX-l-deficient mice. We find that mice with targeted disruption of the COX-1 gene have delayed parturition resulting in neonatal death. Results of matings of COX-l-deficient females with COX-1 intact males, and blastocyst transfer of COX-l-deficient or -intact embryos into wild-type foster mothers, proved necessity and sufficiency of maternal COX-1 for the normal onset of labor. COX-1 expression is induced in gravid murine uterus and by in situ hybridization; this induction is localized to the decidua. Measurement of uterine PGs further confirmed that COX-1 accounted for the majority of PGF2 alpha production. To evaluate the interaction of PGs with oxytocin during murine labor, we generated mice deficient in both oxytocin and COX-I, Surprisingly, the combined oxytocin and COX-l-deficient mice initiated labor at the normal time. COX-l-deficient mice demonstrated impaired luteolysis, as evidenced by elevated serum progesterone concentration and ovarian histology late in gestation, and delayed induction of uterine oxytocin receptors, In contrast, simultaneous oxytocin and COX-1 deficiency restored the normal onset of labor by allowing luteolysis in the absence of elevated PGF2 alpha production, These findings demonstrate that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome the luteotrophic action of oxytocin in late gestation.