Parturition and recruitment of macrophages in cervix of mice lacking the prostaglandin F receptor.
Parturition and recruitment of macrophages in cervix of mice lacking the prostaglandin F receptor.
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缺乏前列腺素 F 受体的小鼠子宫颈中巨噬细胞的分娩和募集。
DOI：
10.1095/biolreprod.107.063404
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发表时间：
2008
影响因子：
3.6
通讯作者：
Sugimoto,Yukihiko
中科院分区：
文献类型：
--
作者：
Yellon,StevenM;Ebner,CharlotteA;Sugimoto,Yukihiko
缺乏前列腺素F受体(Ptgfr(-/-))的转基因小鼠不会分娩，因为黄体溶解被阻止，孕酮的产生持续存在。切除怀孕的Ptgfr(-/-)小鼠的卵巢会导致循环孕酮的下降和活体幼鼠的分娩。本研究的目的是验证Ptgfr(-/-)小鼠的巨噬细胞迁移和宫颈神经支配增加与成熟和分娩有关的假说。对妊娠Ptgfr(-/-)小鼠在妊娠后第15~21天进行宫颈研究，在妊娠第19天摘除卵巢，于妊娠前第20天或出生后约24小时取次日子宫颈。在怀孕第18-19天，巨噬细胞数量和神经纤维密度比未怀孕或怀孕第15天或第21天的Ptgfr(-/-)小鼠增加了3倍以上。这些变化的幅度和时间进程与在繁殖后第19天出生的野生型对照组中发现的类似。因此，延迟分娩的Ptgfr(-/-)小鼠巨噬细胞迁移、神经支配和宫颈重塑的调节机制类似于足月分娩的野生型对照。相比之下，卵巢切除阻止了Ptgfr(-/-)小鼠颈部巨噬细胞的减少。到繁殖后第21天，与怀孕的Ptgfr(-/-)小鼠相比，卵巢切除后巨噬细胞的数量增加了一倍多，而神经纤维密度与出生时相同。这些小鼠的胶原结构密度直接与宫颈的巨噬细胞运输量相匹配。结果表明，前列腺素F(2α)受体和黄体酮撤退是宫颈成熟和分娩过程中最终共同途径的必要组成部分。
Parturition does not occur in transgenic mice lacking the prostaglandin F receptor (Ptgfr (-/-)) because luteolysis is forestalled and progesterone production persists. Ovariectomy of pregnant Ptgfr (-/-) mice leads to a decline in circulating progesterone and delivery of live pups. The objective of the present study was to test the hypothesis that immigration of macrophages and increased innervation of the cervix of Ptgfr (-/-) mice was associated with ripening and parturition. The cervix of pregnant Ptgfr (-/-) mice was studied on Days 15-21 after breeding; additional groups were ovariectomized on Day 19 of pregnancy, and the cervix obtained on Day 20 of pregnancy before birth or the next day at about 24 h after birth. On Days 18-19 of pregnancy, macrophage numbers and nerve fiber density increased more than 3-fold compared with findings in nonpregnant or Day 15 or 21 pregnant Ptgfr (-/-) mice. The magnitude and time course of these changes were comparable to those found in wild-type controls that delivered on Day 19 after breeding. Thus, the mechanism regulating macrophage immigration, innervation, and cervical remodeling in Ptgfr (-/-) mice with delayed parturition is similar to wild-type controls that deliver at term. By contrast, ovariectomy forestalled the decrease in cervical macrophages in Ptgfr (-/-) mice. By Day 21 after breeding, macrophage numbers more than double those after ovariectomy, relative to those found in pregnant Ptgfr (-/-) mice, whereas nerve fiber density was the same regardless of birth. Density of collagen structure in these mice directly matched macrophage traffic in the cervix. The findings indicate that the prostaglandin F (2alpha) receptor and progesterone withdrawal are a necessary part of the final common pathway for ripening of the cervix and the process of parturition.