Sagrillo-Fagundes, Lucas; Assuncao Salustiano, Eugania Maria; Ruano, Rodrigo; Markus, Regina P. et Vaillancourt, Cathy 
ORCID: https://orcid.org/0000-0003-0543-6244
(2018).
Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation
Journal of Pineal Research
, vol. 65
, nº 4: e12520.
pp. 1-14.
DOI: 10.1111/jpi.12520.
Résumé
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% O2 ), thereby inducing differentiation into syncytiotrophoblast that was then exposed to H/R (0.5% O2 , 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 NFκB (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 NFκB 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.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | IL-10; NFκB; TNF; arylalkylamine N-acetyltransferase (AANAT); interleukin (IL)-6; pregnancy; syncytiotrophoblast; villous cytotrophoblasts |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 20 nov. 2019 16:00 |
| Dernière modification: | 16 févr. 2022 15:32 |
| URI: | https://espace.inrs.ca/id/eprint/8168 |
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