The soluble guanylate cyclase inhibitor methylene blue evokes preterm delivery and fetal growth restriction in a mouse model.
BACKGROUND
The present study was undertaken to test whether methylene blue a soluble guanylate cyclase inhibitor, can initiate delivery in the mouse. The potential adverse effects of methylene blue on the fetal growth process were also investigated.


METHODS
ICR (CD-I) mice were injected subcutaneously with Methylene blue at 0 (vehicle), 5, 30, 50, 60 or 85 mg/Kg on gestation days 15.5 and 16 (plug day = gestation day 0).


RESULTS
Methylene blue caused the mice to deliver before gestation day 18 (term gestation). This response was observed in 45%, 50% and 83% of animals receiving Methylene blue at 50, 60 or 85 mg/Kg, respectively (p < 0.05 vs. controls). In a dose-dependent fashion, Methylene blue induced a statistically significant (p < 0.05) derangement of the fetal growth process.


CONCLUSIONS
The present study provides the first evidence that exposure to Methylene blue during late gestation induces preterm delivery and fetal growth restriction. These findings seem to favour the idea that soluble guanylate cyclase and its catalytic product play a role in the control of myometrial contractility and fetal growth process.
Tiboni
G M
GM
Sezione di Ostetricia e Ginecologia, Dipartimento di Medicina e Scienze dell 'Invecchiamento Facoltà di Medicina e Chirurgia, Università G. d'Annunzio, Ospedale Clinicizzato SS. Annunziata, Via dei Vestini, 66013, Chieti, Italy. tiboni@unich.it
Giampietro
F
F
Lamonaca
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D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005317:Fetal Growth Retardation / Q000139:chemically induced*; D005865:Gestational Age; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008751:Methylene Blue / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D009215:Myometrium / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology; D007752:Obstetric Labor, Premature / Q000139:chemically induced*; D009929:Organ Size / Q000187:drug effects; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D011247:Pregnancy; D015430:Weight Gain / Q000187:drug effects
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D008751:Methylene Blue