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ResearchIn-Press PreviewEndocrinologyReproductive biology Open Access | 10.1172/jci.insight.189775

Central SELENOT deficiency impairs gonadotrope axis function, sexual behavior and fertility in male and female mice

Ben Yamine Mallouki,1 Loubna Boukhzar,1 Ludovic Dumont,1 Azénor Abgrall,1 Marjorie Gras,1 Agathe Prieur,1 David Alexandre,1 David Godefroy,1 Yves Tillet,2 Luca Grumolato,1 Nathalie Rives,1 Fatiha Chigr,3 and Youssef Anouar1

1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

Find articles by Mallouki, B. in: PubMed | Google Scholar

1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

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1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

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1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

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1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

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1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

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1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

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1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

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1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

Find articles by Tillet, Y. in: PubMed | Google Scholar

1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

Find articles by Grumolato, L. in: PubMed | Google Scholar

1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

Find articles by Rives, N. in: PubMed | Google Scholar

1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

Find articles by Chigr, F. in: PubMed | Google Scholar

1Neuroendocrine, Endocrine and Germinal Differentiation and Communication La, University of Rouen Normandy, INSERM U1239, Rouen, France

2UMR Physiology of Reproduction and Behavior, INRAE, University of Tours, Tours, France

3Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco

Find articles by Anouar, Y. in: PubMed | Google Scholar |

Published November 6, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.189775.
Copyright © 2025, Mallouki et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 6, 2025 - Version history
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Abstract

Reproductive disorders can result from a defective action of the neuropeptide gonadotropin-releasing hormone (GnRH), the master regulator of reproduction. We have previously shown that SELENOT, a newly-described thioredoxin-like selenoprotein highly expressed in endocrine and neuroendocrine cells, plays a role in hormone secretion and neuroprotection. However, whether SELENOT is involved in neuro-endocrine regulations in vivo is totally unknown. We found that SELENOT deficiency in the brain impaired sexual behavior, leading to a decline in fertility in both male and female mice. Biochemical and histological analyses of the gonadotrope axis of these mice revealed a higher expression of GnRH, which is associated with circulating luteinizing hormone (LH) excess, and elevated steroid hormones in males and a polycystic ovary syndrome (PCOS)-like phenotype in females. In addition, SELENOT deficiency impaired LH pulse secretion in both male and female mice. These alterations are reverted after administration of a GnRH antagonist. Together, our data demonstrate for the first time the role of a selenoprotein in the central control of sexual behavior and reproduction, and identify a new redox effector of GnRH neuron activity impacting both male and female reproductive function.

Version history
  • Version 1 (November 6, 2025): In-Press Preview
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