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other·preclinical research, biomedical research, obstetrics and gynecology, endocrinology·PMC10620973

Differential responses to maternal diabetes in embryo and visceral yolk sac

Frontiers in Cell and Developmental Biology · 4 authors, 2 centres

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The central result was that maternal diabetes exposure induced substantially broader changes in the embryonic transcriptome compared to the yolk sac, highlighting different regulatory mechanisms and identifying novel responsive pathways like cholesterol biosynthesis and NAD metabolism.

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This preclinical study used RNA sequencing to generate unbiased transcriptome profiles of individual embryos and their cognate visceral yolk sacs from the non-obese diabetic (NOD) mouse model at gestational day 8.5. The analysis included morphologically normal specimens with 5 to 9 somite pairs from 33 control and 33 diabetic conceptuses. The central finding was that maternal diabetes exposure had a much greater effect on the transcriptomic profile of the embryo than the yolk sac, revealing that different mechanisms control transcriptional activity in these tissues. The exposure also altered the relationship of many embryonic gene expression levels to developmental progression (somite stage) and identified cholesterol biosynthesis and NAD metabolism as novel responsive pathways. The implications suggest that multiple pathways are affected, which may require broad interventions for prevention.

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other

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preclinical research

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ORIGINAL PAPER

PMC10620973

Differential responses to maternal diabetes in embryo and visceral yolk sac

Frontiers in Cell and Developmental Biology

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ABSTRACT

Introduction: Maternal diabetes during pregnancy is well known to be associated with a higher risk for structural birth defects in the offspring. Recent searches for underlying mechanisms have largely focused on aberrant processes in the embryo itself, although prior research in rodent models implicated dysfunction also of the visceral yolk sac. The objective of our research was to investigate both tissues within the conceptus simultaneously. Methods: We conducted unbiased transcriptome profiling by RNA sequencing on pairs of individual yolk sacs and their cognate embryos, using the non-obese diabetic (NOD) mouse model. The analysis was performed at gestational day 8.5 on morphologically normal specimen to circumvent confounding by defective development. Results: Even with large sample numbers ( n = 33 in each group), we observed considerable variability of gene expression, primarily driven by exposure to maternal diabetes, and secondarily by developmental stage of the embryo. Only a moderate number of genes changed expression in the yolk sac, while in the embryo, the exposure distinctly influenced the relationship of gene expression levels to developmental progression, revealing a possible role for altered cell cycle regulation in the response. Also affected in embryos under diabetic conditions were genes involved in cholesterol biosynthesis and NAD metabolism pathways. Discussion: Exposure to maternal diabetes during gastrulation changes transcriptomic profiles in embryos to a substantially greater effect than in the corresponding yolk sacs, indicating that despite yolk sac being of embryonic origin, different mechanisms control transcriptional activity in these tissues. The effects of maternal diabetes on expression of many genes that are correlated with developmental progression (i.e. somite stage) highlight the importance of considering developmental maturity in the interpretation of transcriptomic data. Our analyses identified cholesterol biosynthesis and NAD metabolism as novel pathways not previously implicated in diabetic pregnancies. Both NAD and cholesterol availability affect a wide variety of cellular signaling processes, and can be modulated by diet, implying that prevention of adverse outcomes from diabetic pregnancies may require broad interventions, particularly in the early stages of pregnancy.

CITATION EXPORT

J. Michael Salbaum, Kirsten P. Stone, Claudia Kruger et al.. Differential responses to maternal diabetes in embryo and visceral yolk sac. Frontiers in Cell and Developmental Biology. (2023). https://doi.org/10.3389/fcell.2023.1273641

AUTHORS

4 · 2 CENTRES

J. Michael Salbaum, Kirsten P. Stone, Claudia Kruger, Claudia Kappen

1 Department of Regulation of Gene Expression, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, United States
2 Department of Developmental Biology, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, United States