A 'minimum dose' of lipopolysaccharide required for implantation failure:: assessment of its effect on the maternal reproductive organs and interleukin-1α expression in the mouse
A 'minimum dose' of lipopolysaccharide required for implantation failure:: assessment of its effect on the maternal reproductive organs and interleukin-1α expression in the mouse
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DOI：
10.1530/rep.1.00110
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发表时间：
2004-07-01
期刊：
影响因子：
3.8
通讯作者：
Jaiswal, YK
中科院分区：
文献类型：
--
作者：
Deb, K;Chaturvedi, MM;Jaiswal, YK
由革兰氏阴性菌引起的生殖道感染会导致流产，是人类妊娠最常见的并发症之一。本研究使用小鼠（Park品系）模型来解释革兰氏阴性细菌脂多糖（LPS）诱导的妊娠丢失的机制。由于LPS的许多生物学效应是由白细胞介素（IL）-1 α介导的，因此研究了IL-1 α在LPS诱导的妊娠丢失中的作用。将妊娠雌性动物腹膜内（i. p.）在妊娠第0.5天给予不同剂量（1至50 μ g）的来自沙门氏菌Re-595的LPS。我们发现，在妊娠第0.5天给予250 μ g/kg体重（即5 μ g/雌性小鼠）的LPS是完全抑制小鼠中胚泡植入所需的“最小剂量”（MD）。该剂量对各种生殖器官（即子宫、外胎盘锥、发育中的胎儿、卵巢等）的病理生理学的影响在妊娠第14天进行评估。通过RT-PCR研究了该剂量对母体子宫角和植入前胚胎中促炎细胞因子IL-1 α表达水平和模式的影响。在妊娠第1天对妊娠雌性i. p.给予单剂量（100 ng/小鼠）重组小鼠IL-1 α，以研究其对着床的影响。我们的研究结果表明，治疗妊娠动物与LPS可能会改变细胞增殖和诱导白细胞浸润，管腔腺上皮变性，增生的各种生殖器官，也可能会改变胚胎和子宫IL-1 α的表达。IL-1 α。给药也引起类似于LPS的着床失败。这些观察结果表明，确定的MD的LPS可能会改变表达的发育重要的促炎细胞因子，如IL-1 α，这可能会反过来，抑制正常的过程中胚泡植入。因此，IL-1 α可能介导了LPS诱导的妊娠动物各生殖器官的组织病理学改变，这可能是小鼠胚泡着床失败的原因之一。
Genital tract infections caused by gram-negative bacteria induce abortion and are one of the most common complications of human pregnancy. This study was carried out to decipher the mechanism of gram-negative bacterial lipopolysaccharide (LPS)-induced pregnancy loss, using a mouse (Park strain) model. Since many of the biological effects of LPS are mediated by interleukin (IL)-1alpha, the role of IL-1alpha in LPS-induced pregnancy loss was studied. Pregnant female animals were injected intraperitoneally (i.p.) with different doses (1 to 50 mug) of LPS from Salmonella minnesota Re-595, on day 0.5 of pregnancy. We found that 250 mug/kg body weight (i.e. 5 mug/female mouse) of LPS when given on day 0.5 of pregnancy was the 'minimum dose' (MD) required to completely inhibit the implantation of the blastocyst in the mouse. The effect of this dose on the pathophysiology of the various reproductive organs (i.e. uterus, ectoplacental cones, developing fetus, ovaries etc.) was assessed on day 14 of pregnancy. The effects of this dose on the level and pattern of expression of the proinflammatory cytokine IL-1alpha in the maternal uterine horns and preimplantation stage embryos were studied by RT-PCR. A single dose (100 ng/mouse) of recombinant mouse IL-1alpha was given i.p. to pregnant females on day 1 of pregnancy to study its effect on implantation. Our results show that treatment of the pregnant animals with LPS may alter cell proliferation and induce leukocyte infiltration, degeneration of luminal glandular epithelium, and hyperplasia in the various reproductive organs, and may also alter both embryonic and uterine IL-1alpha expression. IL-1alpha. administration also caused implantation failure similar to that of LPS. The observations suggest that the determined MD of LPS may alter the expression of developmentally important proinflammatory cytokines such as IL-1alpha, which could, in turn, inhibit the normal processes of blastocyst implantation. Therefore, it is proposed that the LPS-induced histopathological alterations in the various reproductive organs of pregnant animals could be mediated by IL-1alpha and this may be one of the causes of failure of blastocyst implantation in the mouse.