LPS-induced occult loss in mice requires FGL2
LPS-induced occult loss in mice requires FGL2
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DOI：
10.1111/j.1600-0897.2007.00543.x
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发表时间：
2007-12-01
影响因子：
3.6
通讯作者：
Clark, David A.
中科院分区：
文献类型：
--
作者：
Foerster, Katharina;He, Wei;Clark, David A.
问题fgl2凝血酶原是CBA x DBA/2模型的自然流产（再吸收）和由肠炎沙门氏菌脂多糖（LPS）引发的C57Bl/6 （B6）小鼠流产所必需的。与流产不同，B6小鼠的隐性损失在妊娠9.5天之前开始，不需要肿瘤坏死因子α受体1型，可能由肠炎沙门氏菌或大肠杆菌LPS引发。fgl2(+/-) x fgl2(+/-) B6小鼠的杂合交配也有较高的自发性隐性fgl2（-/-）丢失，在较小程度上，滋养细胞和Reichert膜之间出血导致fgl2（+/-）胚胎丢失。然而，这种损失的频率似乎在不同的繁殖时期和不同的实验室之间有所不同。研究人员通过在妊娠第6.5天腹腔注射2 μ g大肠杆菌LPS处理B6 fgl2（+/-） × fgl2（+/-）杂合交配，验证了fgl2缺陷胚胎对LPS的独特易感性。在100 μ L香油中同时皮下注射孕酮2 mg，以确保LPS的作用不是由于抑制卵巢激素的产生。在妊娠第13.5天或分娩后对胚胎进行PCR DNA基因分型。令人惊讶的是，我们发现LPS引起fgl2（+/+）的隐性缺失，在较小程度上fgl2（+/-）的隐性缺失，无论是足月胚胎还是妊娠第13.5天胚胎的PCR分型，这些缺失掩盖了fgl2敲除的效果。结论fgl2（-/-）胚胎自然丢失可能与粘附效应有关，而fgl2（+/+）胚胎易受lps诱导丢失；Fgl2（+/-）胚胎可能受到这两种机制的影响。拮抗FGL2可预防人类和动物的隐秘性妊娠丢失。
ProblemFGL2 prothrombinase is required for spontaneous abortion (resorptions) in the CBA x DBA/2 model, and for abortions in C57Bl/6 (B6) mice triggered by Salmonella enteritidis lipopolysaccharide (LPS). Unlike abortions, occult losses in B6 mice, which begin before gestation day 9.5 in mice, do not require the tumor necrosis factor-alpha receptor type 1, and may be triggered by either Salmonella enteritidis or Escherichia coli LPS. Heterozygous matings of fgl2(+/-) x fgl2(+/-) B6 mice also have a high spontaneous occult loss of fgl2(-/-) and to a lesser extent, fgl2(+/-) embryos caused by hemorrhage between trophoblast and Reichert's membrane. However, the frequency of such losses appears to vary among breeding periods and between laboratories.Method of studyWe tested the hypothesis that FGL2-deficient embryos were uniquely susceptible to LPS by treating B6 fgl2(+/-) x fgl2(+/-) heterozygous matings with 2 mu g E. coli LPS intraperitoneally on day 6.5 of pregnancy. Progesterone 2 mg in 100 mu L sesame oil was administered subcutaneously at the same time to ensure that the effects of the LPS were not because of suppression of ovarian hormone production. PCR DNA genotyping was performed on embryos at day 13.5 of pregnancy, or after parturition.ResultsSurprisingly, we found that LPS caused occult loss of fgl2(+/+), and to a lesser extent fgl2(+/-) embryos, both at term and by PCR typing of embryos at gestation day 13.5, and these losses obscured the effect of fgl2 knockout.ConclusionSpontaneous loss of fgl2(-/-) embryos may relate to adhesion effects, whereas fgl2(+/+) embryos are susceptible to LPS-induced loss; fgl2(+/-) embryos may be affected by both mechanisms. Antagonizing FGL2 could prevent occult pregnancy loss in some human and animal situations.