Format

Send to

Choose Destination
J Pineal Res. 2018 Nov;65(4):e12520. doi: 10.1111/jpi.12520. Epub 2018 Sep 3.

Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation.

Author information

1
INRS-Institut Armand-Frappier and BioMed Research Centre, Laval, Quebec, Canada.
2
Center for Interdisciplinary Research on Well-Being, Health, Society and Environment, Université du Québec à Montréal, Montréal, Quebec, Canada.
3
Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, Minnesota.
4
Department of Physiology, Institute of Bioscience, University of São Paulo (USP), São Paulo, SP, Brazil.

Abstract

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.

KEYWORDS:

IL-10; NFκB; TNF; arylalkylamine N-acetyltransferase (AANAT); interleukin (IL)-6; pregnancy; syncytiotrophoblast; villous cytotrophoblasts

PMID:
30091210
DOI:
10.1111/jpi.12520
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center