Uterine Dysfunction in Diabetic Mice: The Role of Hydrogen Sulfide

It is well-known that the physiological uterine peristalsis, related to several phases of reproductive functions, plays a pivotal role in fertility and female reproductive health. Here, we have addressed the role of hydrogen sulfide (H2S) signaling in changes of uterine contractions driven by diabet...

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Bibliographic Details
Published in:Antioxidants 2020-10, Vol.9 (10), p.917
Main Authors: Mitidieri, Emma, Vanacore, Domenico, Turnaturi, Carlotta, Sorrentino, Raffaella, d’Emmanuele di Villa Bianca, Roberta
Format: Article
Language:English
Subjects:
3-mercaptopyruvate-sulfurtransferase
Animal models
Biosynthesis
Contractility
contraction
Cyclic GMP
Cyclic nucleotides
Diabetes
Diabetes mellitus
Enzymes
Experiments
Fertility
Glucose
Homeostasis
Hydrogen sulfide
Insulin
Menstruation
Morphology
non-obese diabetic mice
Nucleotides
Pathology
Peristalsis
Physiological aspects
Physiology
Potassium
Reproductive health
spontaneous motility
Sulfurtransferase
Uterus
Variance analysis
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Summary:It is well-known that the physiological uterine peristalsis, related to several phases of reproductive functions, plays a pivotal role in fertility and female reproductive health. Here, we have addressed the role of hydrogen sulfide (H2S) signaling in changes of uterine contractions driven by diabetes in non-obese diabetic (NOD) mice, a murine model of type-1 diabetes mellitus. The isolated uterus of NOD mice showed a significant reduction in spontaneous motility coupled to a generalized hypo-contractility to uterotonic agents. The levels of cyclic nucleotides, cAMP and cGMP, notoriously involved in the regulation of uterus homeostasis, were significantly elevated in NOD mouse uteri. This increase was well-correlated with the higher levels of H2S, a non-specific endogenous inhibitor of phosphodiesterases. The exposure of isolated uterus to L-cysteine (L-Cys), but not to sodium hydrogen sulfide, the exogenous source of H2S, showed a weak tocolytic effect in the uterus of NOD mice. Western blot analysis revealed a reorganization of the enzymatic expression with an upregulation of 3-mercaptopyruvate-sulfurtransferase (3-MST) coupled to a reduction in both cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) expression. In conclusion, the increased levels of cyclic nucleotides dysregulate the uterus peristalsis and contractility in diabetic mice through an increase in basal H2S synthesis suggesting a role of 3-MST.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox9100917