Hendrawan Kevin, Whittington Camilla M, Brandley Matthew C, Belov Katherine, Thompson Michael B
School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.
Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Sydney, Australia.
J Exp Zool B Mol Dev Evol. 2017 Jun;328(4):334-346. doi: 10.1002/jez.b.22733. Epub 2017 Mar 10.
The evolutionary transition from egg-laying to live-bearing in amniote vertebrates (reptiles and mammals) requires the development of a closer association between the maternal and embryonic tissue to facilitate gas and nutrient exchange with the embryo. Because the embryo is an allograft to the father and mother, it could be considered foreign by the maternal immune system and thus be immunologically rejected during pregnancy. In eutherian ("placental") mammals, the proinflammatory genes interleukin 1B (IL1B), tumor necrosis factor (TNF) and tumor necrosis factor receptor superfamily 1A (TNFRSF1A) are tightly regulated in the pregnant uterus to prevent embryonic rejection. We tested whether inflammation is similarly regulated in pregnant viviparous reptiles by comparing the expression of IL1B, TNF, and TNFRSF1A in the pregnant and nonpregnant uterus of the viviparous lizard, Pseudemoia entrecasteauxii. We found statistically significant support for the downregulation of pregnant uterine TNF mRNA expression in P. entrecasteauxii, but no statistically significant changes in mRNA expression of TNFRSF1A or IL1B between pregnant and nonpregnant uteri. Although these genes are apparently not regulated at the transcriptional level, our immunofluorescence microscopy analyses nonetheless demonstrate that the IL1B proteins are stored intracellularly during pregnancy, possibly resulting in inhibition of inflammatory response. We therefore conclude that processes of both transcriptional (TNF) and posttranslational (IL1B) gene regulation may reduce inflammation in the pregnant uterus of this viviparous reptile. Our study is important because it demonstrates that regulating the maternal immune system to prevent embryonic rejection may be important in reptilian pregnancy as it is in mammalian pregnancy.
羊膜动物脊椎动物（爬行动物和哺乳动物）从卵生到胎生的进化转变需要母本和胚胎组织之间建立更紧密的联系，以促进与胚胎的气体和营养物质交换。由于胚胎对于父母来说是同种异体移植，它可能被母本免疫系统视为外来物，从而在怀孕期间被免疫排斥。在真兽亚纲（“胎盘”）哺乳动物中，促炎基因白细胞介素1B（IL1B）、肿瘤坏死因子（TNF）和肿瘤坏死因子受体超家族1A（TNFRSF1A）在怀孕子宫中受到严格调控，以防止胚胎被排斥。我们通过比较胎生蜥蜴恩氏伪蜥怀孕和未怀孕子宫中IL1B、TNF和TNFRSF1A的表达，来测试怀孕的胎生爬行动物中炎症是否受到类似的调控。我们发现恩氏伪蜥怀孕子宫中TNF mRNA表达下调有统计学意义的支持，但怀孕和未怀孕子宫之间TNFRSF1A或IL1B的mRNA表达没有统计学意义的变化。尽管这些基因显然在转录水平不受调控，但我们的免疫荧光显微镜分析表明，IL1B蛋白在怀孕期间储存在细胞内，可能导致炎症反应受到抑制。因此，我们得出结论，转录（TNF）和翻译后（IL1B）基因调控过程可能会减轻这种胎生爬行动物怀孕子宫中的炎症。我们的研究很重要，因为它表明调节母本免疫系统以防止胚胎被排斥在爬行动物怀孕中可能像在哺乳动物怀孕中一样重要。
