Altered gene expression and spongiotrophoblast differentiation in placenta from a mouse model of diabetes in pregnancy.

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.

Methods: 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.

Results: 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.