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Volume 15
Issue 11
10.3390/metabo15110699
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Article

Melatonin and Inflammatory Cytokines as Modulators of the Interaction Between Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence

by
Danielle Cristina Honório França
1,
Eduardo Luzia França
2,
Adenilda Cristina Honório-França
2,*,
Kênia Maria Rezende Silva
2,
Adriele Ataídes de Queiroz
2,
Tassiane Cristina Morais
3,
Emanuelle Carolina Honorio França
2,
Carolina Neiva Frota de Carvalho
1,
Danny Laura Gomes Fagundes-Triches
2,
Angélica Mércia Pascon Barbosa
1,4,
Iracema de Mattos Paranhos Calderon
1,
Luis Sobrevia
1,5,6,7 and
Marilza Vieira Cunha Rudge
1,*
1
Department of Gynecology and Obstetrics, Botucatu Medical School (FMB), São Paulo State University (UNESP), Botucatu 18618-687, Brazil
2
Institute of Biological and Health Science, Federal University of Mato Grosso (UFMT), Barra do Garças 78605-091, Brazil
3
School of Sciences, Santa Casa de Misericórdia de Vitória (EMESCAM), Vitória 29045-402, Brazil
4
Department of Physiotherapy and Occupational Therapy, School of Philosophy and Sciences, São Paulo State University (UNESP), Marilia 17525-900, Brazil
5
Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
6
Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, E-41012 Seville, Spain
7
Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Australia
*
Authors to whom correspondence should be addressed.
Metabolites 2025, 15(11), 699; https://doi.org/10.3390/metabo15110699
Submission received: 25 September 2025 / Revised: 23 October 2025 / Accepted: 25 October 2025 / Published: 28 October 2025
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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Abstract

Background: The pathogenesis of developing gestational diabetes mellitus (GDM) integrated with pregnancy-specific urinary incontinence (PSUI) may be related to immunological and hormonal factors. Inflammatory cytokines influence the function and regulation of the urinary tract, and changes in melatonin concentration are a predisposing factor for smooth muscle dysfunction and cystometric changes. Objective: This study examines the influence of melatonin, MT1 and MT2 receptors, and inflammatory cytokines in the blood and urine of pregnant women with GDM and PSUI. Methods: Two hundred sixty-nine pregnant women were approached during the diagnostic investigation of GDM and answered a specifically structured questionnaire about the involuntary loss of urine. According to these criteria, mothers were divided into four groups: continent normoglycemic (NG-C), incontinent normoglycemic (NG-I), continent GDM (GDM-C), and incontinent GDM (GDM-UI). Blood and urine samples were collected to determine the levels of melatonin, melatonin sulfate, melatonin receptors (MT1 and MT2), and inflammatory cytokines. Results: Blood level of melatonin and IL-10 was lower, but MT1, MT2, IL-1β, IL-8, and TNF-α were higher in GDM-UI compared with the NG-C group. The melatonin sulfate level was lower in the urine of the GDM-UI group compared with the NG-C group. Conclusions: Maternal hyperglycemia associated with urinary incontinence generates an inflammatory environment characterized by reduced melatonin and IL-10 and increased IL-1β, IL-8, and TNF-α in the blood of mothers with GDM with UI. This environmental condition may be involved in the pathogenesis of these pathologies.
Keywords: neuropharmacology; hormones; hyperglycemia; involuntary loss of urine; hormone receptor; immunomodulation; gestation; diabetes neuropharmacology; hormones; hyperglycemia; involuntary loss of urine; hormone receptor; immunomodulation; gestation; diabetes
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MDPI and ACS Style

França, D.C.H.; França, E.L.; Honório-França, A.C.; Silva, K.M.R.; Queiroz, A.A.d.; Morais, T.C.; França, E.C.H.; de Carvalho, C.N.F.; Fagundes-Triches, D.L.G.; Barbosa, A.M.P.; et al. Melatonin and Inflammatory Cytokines as Modulators of the Interaction Between Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence. Metabolites 2025, 15, 699. https://doi.org/10.3390/metabo15110699

AMA Style

França DCH, França EL, Honório-França AC, Silva KMR, Queiroz AAd, Morais TC, França ECH, de Carvalho CNF, Fagundes-Triches DLG, Barbosa AMP, et al. Melatonin and Inflammatory Cytokines as Modulators of the Interaction Between Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence. Metabolites. 2025; 15(11):699. https://doi.org/10.3390/metabo15110699

Chicago/Turabian Style

França, Danielle Cristina Honório, Eduardo Luzia França, Adenilda Cristina Honório-França, Kênia Maria Rezende Silva, Adriele Ataídes de Queiroz, Tassiane Cristina Morais, Emanuelle Carolina Honorio França, Carolina Neiva Frota de Carvalho, Danny Laura Gomes Fagundes-Triches, Angélica Mércia Pascon Barbosa, and et al. 2025. "Melatonin and Inflammatory Cytokines as Modulators of the Interaction Between Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence" Metabolites 15, no. 11: 699. https://doi.org/10.3390/metabo15110699

APA Style

França, D. C. H., França, E. L., Honório-França, A. C., Silva, K. M. R., Queiroz, A. A. d., Morais, T. C., França, E. C. H., de Carvalho, C. N. F., Fagundes-Triches, D. L. G., Barbosa, A. M. P., Calderon, I. d. M. P., Sobrevia, L., & Rudge, M. V. C. (2025). Melatonin and Inflammatory Cytokines as Modulators of the Interaction Between Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence. Metabolites, 15(11), 699. https://doi.org/10.3390/metabo15110699

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