Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse.
Effect of Pregnancy and Delivery on Cytokine Expression in a Mouse Model of Pelvic Organ Prolapse.
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妊娠和递送对骨盆器官脱垂小鼠模型中细胞因子表达的影响。
DOI：
10.1097/spv.0000000000000394
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发表时间：
2017
影响因子：
1.6
通讯作者：
Damaser MS
中科院分区：
文献类型：
--
作者：
Couri BM;Lenis AT;Borazjani A;Balog BM;Kuang M;Butler RS;Penn MS;Damaser MS
本研究的目的是确定妊娠和分娩方式对赖氨酰氧化酶样1基因敲除（Loxl 1 KO）小鼠盆腔器官和血清中细胞因子表达的影响，这些小鼠在分娩后发生盆腔器官脱垂（POP）。从怀孕期间、阴道分娩或剖腹产后以及假剖腹产和未操作对照的雌性Loxl 1 KO小鼠中采集膀胱、尿道、阴道、直肠和血液。还从妊娠和阴道分娩的野生型（WT）小鼠和未处理的雌性未交配WT对照小鼠中收获盆腔器官和血液。使用qRT-PCR和/或ELISA评估标本。与妊娠WT小鼠相比，妊娠Loxl 1 KO小鼠的阴道、尿道、膀胱和直肠中Cxcl 12和Ccl 7 mRNA均显著上调，表明Loxl 1 KO小鼠中这两种细胞因子的系统性失调是对妊娠的反应。Loxl 1 KO和WT小鼠在妊娠期细胞因子表达的差异在阴道分娩后持续存在。与妊娠小鼠相比，Loxl 1 KO小鼠中Ccl 7基因表达增加更快且程度更大，转化为阴道分娩后Loxl 1 KO小鼠血清中Ccl 7的持续增加更长。Loxl 1 KO小鼠对妊娠的细胞因子反应增加，可能是因为它们不太能够改革和重新交联拉伸的弹性蛋白以适应幼崽，并且这种所得组织在妊娠期间拉伸。分娩后CCL 7的上调可以提供分娩损伤水平的指标，尿道和阴道似乎特别容易受到伤害。
The aim of this study was to determine the effect of pregnancy and delivery mode on cytokine expression in the pelvic organs and serum of lysyl oxidase like-1 knockout (Loxl1 KO) mice, which develop pelvic organ prolapse (POP) after delivery. Bladder, urethra, vagina, rectum and blood were harvested from female Loxl1 KO mice during pregnancy, after vaginal or cesarean delivery, and from sham cesarean and unmanipulated controls. Pelvic organs and blood were also harvested from pregnant and vaginally delivered wild-type (WT) mice and from unmanipulated female virgin WT controls. Specimens were assessed using qRT-PCR and/or ELISA. Both Cxcl12 and Ccl7 mRNA were significantly upregulated in the vagina, urethra, bladder, and rectum of pregnant Loxl1 KO mice compared to pregnant WT mice, suggesting systemic dysregulation of both of these cytokines in Loxl1 KO mice as a response to pregnancy. The differences in cytokine expression between Loxl1 KO and WT mice in pregnancy persisted after vaginal delivery. Ccl7 gene expression increases faster and to a greater extent in Loxl1 KO mice, translating to longer lasting increases in CCL7 in serum of Loxl1 KO mice after vaginal delivery, compared to pregnant mice. Loxl1 KO mice have an increased cytokine response to pregnancy, perhaps because they are less able to reform and re-crosslink stretched elastin to accommodate pups and this resultant tissue stretches during pregnancy. Upregulation of CCL7 after delivery could provide an indicator of level of childbirth injury, to which the urethra and vagina appear to be particularly vulnerable.