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Aljani, B.* ; Garbe, A.I.* ; Sedlmeier, E.-M. ; Lickert, R. ; Rost, F.* ; Ziegler, A.-G. ; Bonifacio, E. ; Eugster, A.*

Gene expression profiles in placenta and their association with anesthesia, delivery mode and maternal diabetes.

Placenta 158, 126-135 (2024)

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INTRODUCTION: Fetal development is dependent on placenta and affected by multiple factors including maternal diabetes. Here we aimed to identify maternal diabetes-associated changes in placentas and analyzed placental gene expression to understand its modulation by maternal diabetes and birth mode. METHODS: Placental RNAseq transcriptome analyses were performed on maternally-derived decidua and fetal-derived villous tissue from pregnancies of mothers with type 1 diabetes (n = 14), gestational diabetes (n = 6) and without diabetes (n = 14). Information on delivery mode and anesthesia were included as covariables. Analyses were performed separately for decidua and fetal tissues and adjusted for sex. RESULTS: Substantial placenta gene expression variation was associated with factors other than maternal diabetes, including site, sex, anesthesia type and delivery mode. Two dominant gene expression clusters aligned to anesthesia and delivery mode were observed for decidua and villous tissue. Upregulation of genes within pathways related to organ morphogenesis and downregulation of immune response to steroid- and hypoxia pathway genes was characteristic of placentas from primary cesarean section deliveries with spinal anesthesia. Opposite profiles were observed for placentas from secondary cesarean and epidural anesthesia deliveries. Placentas from vaginal delivery had intermediate gene expression profiles. More subtle changes were associated with maternal diabetes: upregulation of ribosome activity, down-regulation of maternally-derived decidua chemokine signaling pathways and for gestational diabetes, alteration in hypoxia response genes. DISCUSSION: The findings reveal suppression of immune pathways and upregulation of ribosome activity in the placenta by maternal diabetes highlighting the importance of confounding factors when examining cell and tissue expression profiles. Further studies should determine whether the observed gene expression differences are related to underlying causes for cesarean section deliveries.

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