Journal
JOURNAL OF PINEAL RESEARCH
Volume 65, Issue 4, Pages -Publisher
WILEY
DOI: 10.1111/jpi.12520
Keywords
arylalkylamine N-acetyltransferase (AANAT); IL-10; interleukin (IL)-6; NF kappa B; pregnancy; syncytiotrophoblast; TNF; villous cytotrophoblasts
Categories
Funding
- Natural Sciences and Engineering Research Council of Canada [262011-2009]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
- Programme de bourses d'excellence pour etudiants etrangers du Ministere de l'Education
- Reseau Quebecois en Reproduction-FRQNT
- Fondation Armand Frappier
- Reseau Quebecois en reproduction
- de l'Enseignement superieurs et de la recherche (MEESR)-Fonds de recherche du Quebec-Nature et technologies
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Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin levels in the placenta and maternal plasma. However, the effects of exogenous melatonin on inflammation and autophagy induced by pregnancy complications associated with H/R await investigation. This study aimed to determine as to whether melatonin protects human primary villous trophoblasts against H/R-induced autophagy, inflammation, and apoptosis. Human primary villous cytotrophoblasts were isolated and immunopurified from normal term placentas. These cells were then exposed or not to 1 mmol/L melatonin for 72 hour in normoxia (8% O-2), thereby inducing differentiation into syncytiotrophoblast that was then exposed to H/R (0.5% O-2, for 4 hour) or normoxia. H/R decreased endogenous melatonin synthesis (by 68%) and interleukin (IL)-10 levels (by 72%), coupled to increased tumor necrosis factor (TNF) (by 114%), IL-6 (by 55%), and NF kappa B (by 399%), compared to normoxia. Melatonin treatment reversed the H/R effect, restoring IL-10, TNF, and IL-6 levels to those of the normoxia condition. Melatonin, as well as NF kappa B inhibition, enhanced autophagy activation, consequently increasing syncytiotrophoblast survival in H/R conditions. This study suggests that H/R, which is present in pregnancy complications, inhibits endogenous melatonin production, thereby contributing to reduced syncytiotrophoblast viability. Results indicate that exogenous melatonin treatment may afford protection against H/R-induced damage, thereby enhancing placental cell survival, and contributing to improved fetal outcomes.
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