REVIEW article
Front. Endocrinol.
Sec. Neuroendocrine Science
Neuroactive Steroids in the Programming of Neurodevelopment: Implications of Maternal Obesity
Provisionally accepted
Carmen J. Zamora-Sánchez1
Juan Carlos González-Orozco2Jonatan Mendoza-Ortega3Mariana L. Villegas-Soto4
Ignacio Camacho-Arroyo4
Guadalupe Estrada-Gutierrez1*- 1Department of Immunobiochemistry, National Institute of Perinatology, Mexico City, Mexico
- 2Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston Texas, United States
- 3Departamento de Inmunología, Instituto Politecnico Nacional Escuela Nacional de Ciencias Biologicas, Mexico City, Mexico
- 4Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico
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Neuroactive steroids synthesized within the maternal-placental-fetal unit play a crucial role in fetal neurodevelopment by regulating cell proliferation, migration, and myelination, neurogenesis, gliogenesis, and synaptogenesis, ultimately shaping brain maturation. Dysregulation of neuroactive steroid metabolism, receptor signaling, and downstream pathways has been linked to neurodevelopmental and mood disorders. Maternal overweight and obesity, increasingly prevalent worldwide, induce profound metabolic and hormonal adaptations that may interfere with neuroactive steroid synthesis and function. These disturbances are associated with a higher risk of autism spectrum disorder, attention deficit hyperactivity disorder, and cognitive impairments in offspring, frequently with sex-specific effects. Despite these observations, the impact of obesity on neuroactive steroid levels and their regulatory roles during pregnancy remains poorly understood. This review synthesizes preclinical and clinical evidence on the biosynthesis, mechanisms of action, and neurodevelopmental effects of neuroactive steroids during the critical window of fetal programming. Furthermore, it highlights a current knowledge on how maternal overweight and obesity alter neuroactive steroid metabolism within the maternal–placental–fetal unit and explores their potential contribution to adverse neurodevelopmental outcomes. Addressing these knowledge gaps may uncover novel biomarkers and therapeutic targets to improve neurodevelopmental trajectories in populations increasingly exposed to maternal metabolic comorbidities.
Keywords: neuroplacentology, Neurosteroids, Pregnancy, fetal programming, Allopregnanolone, steroid metabolism, Body Mass Index, maternal obesity
Received: 10 Sep 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Zamora-Sánchez, González-Orozco, Mendoza-Ortega, Villegas-Soto, Camacho-Arroyo and Estrada-Gutierrez. 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: Guadalupe Estrada-Gutierrez, gpestrad@gmail.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.