Intrauterine bacterial inoculation induces labor in the mouse by mechanisms other than progesterone withdrawal
Intrauterine bacterial inoculation induces labor in the mouse by mechanisms other than progesterone withdrawal
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DOI：
10.1095/biolreprod67.4.1337
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发表时间：
2002-10-01
影响因子：
3.6
通讯作者：
Muhle, R
中科院分区：
文献类型：
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作者：
Hirsch, E;Muhle, R
我们验证了孕酮(P-4)停用是宫内细菌引起小鼠早产的主要机制的假设。妊娠14.5天的CD-1小鼠接受四种治疗之一：1)宫内注射无菌介质，2)宫内注射106个热灭活大肠杆菌，3)宫内注射109个热灭活大肠杆菌，或4)卵巢切除。于术后0.75~11h的4个时间点处死小鼠，采集血清。另外，动物分别接受S.C.P-4或在卵巢切除或大剂量细菌接种前2小时与赋形剂一起接种。与对照组相比，卵巢切除组血清P4水平在1h和8h分别下降了60%和81%(P<；0.001)。相比之下，宫内接种109株细菌后，P-4下降幅度较小，8h仅下降28%(P=0.24，与低于早产阈值的106株菌无显著差异)。尽管卵巢切除组P4水平显著降低，但宫内有109个细菌的分娩时间显著缩短(24 5.6 h比19 3.6 h，P=0.03)。每只小鼠1.5 mg P-4的预处理延长了卵巢切除和大剂量细菌注射后分娩的间隔时间，与药理学上升高的血清P-4水平有关。相比之下，生理性补充P-4(每只小鼠0.375毫克)仅在卵巢切除组延长妊娠。我们的结论是，在小鼠宫内接种细菌后，内源性P-4的退出不是分娩的主要原因。
We tested the hypothesis that progesterone (P-4) withdrawal is the primary mechanism by which intrauterine bacteria induce preterm labor in mice. CD-1 mice on Day 14.5 of a 19- to 20-day gestation were subjected to one of four treatments: 1) intrauterine injection of sterile medium, 2) intrauterine injection of 106 heat-killed Escherichia coli bacteria, 3) intrauterine injection of 109 heat-killed E coli, or 4) ovariectomy. Mice were then killed at four time points from 0.75 to 11 h after surgery for serum collection. Separately, animals were pretreated either with s.c. P-4 or with vehicle 2 h before ovariectomy or high-dose bacterial inoculation. Ovariectomy led to a rapid fall in serum P4 levels of 60% by 1 h and 81 % by 8 h compared with levels in controls (P < 0.001). In contrast, intrauterine inoculation with 109 bacteria led to a more modest decline in P-4 of only 28% by 8 h (P = 0.24, which was no different from that of 106 bacteria, an inoculum below the threshold for preterm delivery). Despite significantly lower levels of P4 in the ovariectomy group, time to delivery was significantly shorter with 109 bacteria intrauterine (24 5.6 h vs. 19 3.6 h, P = 0.03). Pretreatment with 1.5 mg P-4 per mouse prolonged the interval to delivery following both ovariectomy and high-dose bacteria, in association with pharmacologically elevated serum P-4 levels. In contrast, physiologic P-4 supplementation (0.375 mg/mouse) prolonged gestation only in the ovariectomy group. We conclude that withdrawal of endogenous P-4 is not the primary cause of labor following intrauterine bacterial inoculation in mice.