Potential Mechanisms Involved in Diabetic Teratogenesis During Embryonic Neural Tube Closure

Janice Block

doi:10.31487/j.jdmc.2019.01.06

Abstract

Diabetes mellitus during pregnancy is a risk factor for improper closure of the neural tube during embryonic development. It is likely that this occurs via several parallel pathways. Previously proposed pathways for diabetic teratogenesis during neural tube closure include augmented production of nitric acid; reduction of Pax3; and increased production of long-chain acyl-CoA synthetase 1 (ACSL1). In the current discussion, an additional hypothesis is offered: that hyperglycemia might exert its teratogenic effects on the developing embryo via overexpression of collagen IV, leading to collagen imbalance and errors of remodelling.

Highlights

Diabetes mellitus during pregnancy is a known risk factor for imperfect closure of the developing embryonic neural tube
Proposed pathways for diabetic teratogenesis during neural tube closure have included augmented production of nitric acid, which is toxic in excess to the developing neural tube; reduction of Pax3, which suppresses p53 dependent cell death during embryonic development of the neural tube; and increased production of long-chain acyl-CoA synthetase 1 (ACSL1), which promotes polarization of macrophages or toward a more inflammatory phenotype
It is of interest that all of the three mechanisms suspected to be involved in diabetic teratogenesis above -- Pax3 reduction, nitric acid excess, and ACSL1 upregulation -- should reduce the population of macrophages belonging the M2 or M2-like phenotype (Hereafter, “M2” includes “M2like” in the text below.) A reduction in Pax3 would be expected to result in fewer M2 macrophages via promotion of p53 associated polarization to the M1 phenotype

Summary

Introduction

Diabetes mellitus during pregnancy is a known risk factor for imperfect closure of the developing embryonic neural tube. It is of interest that all of the three mechanisms suspected to be involved in diabetic teratogenesis above -- Pax3 reduction, nitric acid excess, and ACSL1 upregulation -- should reduce the population of macrophages belonging the M2 or M2-like phenotype (Hereafter, “M2” includes “M2like” in the text below.) A reduction in Pax3 would be expected to result in fewer M2 macrophages via promotion of p53 associated polarization to the M1 phenotype.

Results

Conclusion