Laboratory of Regulation of Gene Expression, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Diabetologia. 2011 Jul;54(7):1909-20. doi: 10.1007/s00125-011-2132-6. Epub 2011 Apr 14.
AIMS/HYPOTHESIS: Pregnancies complicated by diabetes have a higher risk of adverse outcomes for mothers and children, including predisposition to disease later in life, e.g. metabolic syndrome and hypertension. We hypothesised that adverse outcomes from diabetic pregnancies may be linked to compromised placental function, and sought to identify cellular and molecular abnormalities in diabetic placenta.
Using a mouse model of diabetic pregnancy, placental gene expression was assayed at mid-gestation and cellular composition analysed at various stages. Genome-wide expression profiling was validated by quantitative PCR and tissue localisation studies were performed to identify cellular correlates of altered gene expression in diabetic placenta.
We detected significantly altered gene expression in diabetic placenta for genes expressed in the maternal and those expressed in the embryonic compartments. We also found altered cellular composition of the decidual compartment. In addition, the junctional and labyrinth layers were reduced in diabetic placenta, accompanied by aberrant differentiation of spongiotrophoblast cells.
CONCLUSIONS/INTERPRETATION: Diabetes during pregnancy alters transcriptional profiles in the murine placenta, affecting cells of embryonic and maternal origin, and involving several genes not previously implicated in diabetic pregnancies. The molecular changes and abnormal differentiation of multiple cell types precede impaired growth of junctional zone and labyrinth, and of placenta overall. Regardless of whether these changes represent direct responses to hyperglycaemia or are physiological adaptations, they are likely to play a role in pregnancy complications and outcomes, and to have implications for developmental origins of adult disease.
目的/假设：患有糖尿病的妊娠会增加母婴不良结局的风险，包括晚年易患代谢综合征和高血压等疾病。我们假设糖尿病妊娠的不良结局可能与胎盘功能受损有关，并试图确定糖尿病胎盘的细胞和分子异常。
使用糖尿病妊娠的小鼠模型，在妊娠中期检测胎盘基因表达，并在不同阶段分析细胞组成。通过定量 PCR 验证全基因组表达谱，并进行组织定位研究，以确定糖尿病胎盘改变基因表达的细胞相关性。
我们检测到母体和胚胎部位表达的基因在糖尿病胎盘中有明显改变的基因表达。我们还发现蜕膜部位的细胞组成发生了改变。此外，糖尿病胎盘的合体滋养层和细胞滋养层减少，伴有海绵滋养层细胞的异常分化。
结论/解释：妊娠期间的糖尿病改变了小鼠胎盘的转录谱，影响了胚胎和母体来源的细胞，并涉及到一些以前未被认为与糖尿病妊娠有关的基因。多种细胞类型的分子变化和异常分化先于合体带和细胞滋养层以及整个胎盘生长不良。无论这些变化是直接对高血糖的反应还是生理适应，它们都可能在妊娠并发症和结局中发挥作用，并对成人疾病的发育起源产生影响。
