ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Diabetes: Molecular Mechanisms

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1564441

This article is part of the Research TopicPlacental Dysfunction in Pregnancy: Endocrine and Metabolic Mechanisms in Preeclampsia, FGR, Diabetes, and HypertensionView all articles

Maternal Diabetes Disrupts Early Corticogenesis Through Altered Mitotic Gene Regulation: A Transcriptomic Analysis

Provisionally accepted
  • Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología (INPER), Mexico City, Mexico

The final, formatted version of the article will be published soon.

Maternal diabetes is associated with neurodevelopmental impairments in offspring, but the underlying molecular mechanisms remain unclear. This study investigates the early effects of maternal diabetes on cortical neurogenesis, focusing on the mitotic processes in embryos from diabetic rats. Using RNA sequencing of the dorsal prosencephalon from 12-day-old embryos (E12) without neural tube defects, we identified 247 differentially expressed genes (111 up-regulated, 136 down-regulated). Gene ontology analysis revealed that the most enriched pathways in the upregulated genes were related to mitosis, microtubule organization, and chromosome segregation, with Aurkb and Numa1 being central regulators. These two upregulated genes were validated through qRT-PCR but not through Western blot. However, immunofluorescence showed changes in cell distribution of NUMA1 and AURKB, evidencing abnormal mitotic spindle architecture to E12, characterized by monopolar spindles and increased asymmetric cell division in neural stem cells, suggesting an early shift towards neurogenesis. These findings indicate that maternal diabetes disrupts mitotic regulation and accelerates neurogenesis, potentially depleting the neural stem cell pool and impairing cortical development. The findings here provide a possible mechanism contributing to cognitive and motor deficits observed in the offspring of diabetic mothers.

Keywords: Maternal diabetes, embryo cortical transcriptome, corticogenesis, neural stem cells mitosis, achromatic spindle

Received: 21 Jan 2025; Accepted: 11 Apr 2025.

Copyright: © 2025 Bautista, de la Merced-Garcia, Díaz-Piña, Diaz, Avila-González and Molina-Hernández. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Anayansi Molina-Hernández, Fisiología y Desarrollo Celular, Instituto Nacional de Perinatología (INPER), Mexico City, Mexico

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