Glucose, Insulin and Oxygen Modulate Expression of Serotonin-Regulating Genes in Human First-Trimester Trophoblast Cell Line ACH-3P

Perić, Maja; Horvatiček, Marina; Tandl, Veronika; Bečeheli, Ivona; Majali‐Martinez, Alejandro; Desoyé, Gernot; Štefulj, Jasminka

doi:10.3390/biomedicines11061619

Cited by 2 publications

(1 citation statement)

References 60 publications

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“…Gestational diabetes mellitus (GDM) is an important metabolic disease with increased insulin counter-regulatory hormones generating glucose intolerance, an inflammatory environment, abnormalities in oxidative stress, and altering the profile of released cytokines and other hormones [1,2].…”

Section: Introductionmentioning

confidence: 99%

Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence

França,

Honorio-França,

Silva

et al. 2023

IJMS

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Serotonin and interleukin 10 (IL-10) may play a role in gestational diabetes mellitus. Hyperglycemic environment, the detrusor musculature of the bladder and pelvic floor muscles may become damaged, leading to urination problems and urine viscosity in pregnant women with gestational diabetes mellitus and pregnancy-specific urinary incontinence. Urine and blood samples were collected from pregnant women between 24 and 28 weeks of gestation. The serotonin concentration and cytokine IL-10 levels were evaluated in plasma and urine. In the total blood and urine, the viscosity was evaluated in the presence and absence of exogenous serotonin and IL-10. The plasma serotonin levels decreased, while the urine serotonin levels increased in the normoglycemic incontinent (NG-I), hyperglycemic continent (GDM-C), and hyperglycemic incontinent (GDM-I) groups. The IL-10 in the plasma decreased in the GDM-I group and was higher in the urine in the NG-I and GDM-I groups. The blood viscosity was higher, independently of urinary incontinence, in the GDM groups. The serotonin increased the blood viscosity from women with GDM-C and urine in the NG-I, GDM-C, and GDM-I groups. Blood and urine in the presence of IL-10 showed a similar viscosity in all groups studied. Also, no difference was observed in the viscosity in either the blood or urine when in the presence of serotonin and IL-10. These findings suggest that serotonin and IL-10 have the potential to reduce blood viscosity in pregnant women with gestational diabetes and specific urinary incontinence, maintaining values similar to those in normoglycemic women’s blood.

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Section: Introductionmentioning

confidence: 99%

Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence

França,

Honorio-França,

Silva

et al. 2023

IJMS

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MCM proteins are up-regulated in placentas of women with reduced insulin sensitivity

Bandres-Meriz,

Sanz-Cuadrado,

Hurtado de Mendoza

et al. 2024

Bioscience Reports

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In the first trimester of pregnancy the human placenta grows rapidly, making it sensitive to changes in the intrauterine environment. To test whether exposure to an environment in utero often associated with obesity modifies placental proteome and function, we performed untargeted proteomics (LC-MS/MS) in placentas from 19 women (gestational age 35-48 days). Maternal clinical traits (body mass index, leptin, glucose, C-peptide and insulin sensitivity) and gestational age were recorded. DNA replication and cell cycle pathways were enriched in the proteome of placentas of women with low maternal insulin sensitivity. Driving these pathways were the minichromosome maintenance (MCM) proteins MCM2-7 (MCM-complex). These proteins are part of the pre-replicative complex and participate in DNA damage repair. Indeed, MCM6 and γH2AX (DNA-damage marker) protein levels correlated in first trimester placental tissue (r=0.514, p<0.01). MCM6 and γH2AX co-localized to nuclei of villous cytotrophoblast cells, the proliferative cell type of the placenta, suggesting increased DNA damage in this cell type. To mimic key features of the intrauterine obesogenic environment, a first trimester trophoblast cell line, i.e., ACH-3P, was exposed to high insulin (10nM) or low oxygen tension (2.5% O2). There was a significant correlation between MCM6 and γH2AX protein levels, but these were independent of insulin or oxygen exposure. These findings show that chronic exposure in utero to reduced maternal insulin sensitivity during early pregnancy induces changes in the early first trimester placental proteome. Pathways related to DNA replication, cell cycle and DNA damage repair appear especially sensitive to such an in utero environment.

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Glucose, Insulin and Oxygen Modulate Expression of Serotonin-Regulating Genes in Human First-Trimester Trophoblast Cell Line ACH-3P

Cited by 2 publications

References 60 publications

Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence

Serotonin and Interleukin 10 Can Influence the Blood and Urine Viscosity in Gestational Diabetes Mellitus and Pregnancy-Specific Urinary Incontinence

MCM proteins are up-regulated in placentas of women with reduced insulin sensitivity

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