Type 1 diabetes was very poor with high rates of serious complications including miscarriages, congenital malformations, and stillbirths, even with the more intensive control of blood glucose pre-pregnancy.
The glucose and HIF-1 signaling is dysregulated in diabetes, maternal glucose and oxygen are transferred to the fetus across the placenta down a concentration gradient. Therefore, we set out to investigate how diabetes in pregnancy affects the trophoblast implantation, proliferation, invasion, villous differentiation, and placental mass expansion by combining histological features and expression and DNA accessibility profiles from multiple fetal and adult tissues in STZ-induced T1D mice.
From the project last year, we didn’t detect any significant changes by chromic mild hyperglycemia in mouse and human oocytes. For placentas and vessels, we have detected strong transcriptional signatures that we now are investigating further for functionality. Moreover, our findings have led us in other directions, away from the HIF-1 pathway. We are now primarily focusing on the effects of maternal T1D on **offspring** phenotype and have several interesting findings that will be followed up in the coming year.
We will continue to sequence RNA abundance from liver, muscle, and adipose tissues from control and hyperglycemic offspring. We will dissect and collect samples at 4 time points: fetal, young age, adulthood, and old age for both female and male offspring and sequence the total RNA and DNA accessibility from these samples.