000168371 001__ 168371
000168371 005__ 20260204153543.0
000168371 0247_ $$2doi$$a10.1530/RAF-25-0084
000168371 0248_ $$2sideral$$a147835
000168371 037__ $$aART-2025-147835
000168371 041__ $$aeng
000168371 100__ $$aViola, Irene
000168371 245__ $$aMelatonin mitigates autophagy: unlocking conditional resilience in sheep trophoblast cells exposed to a hypoxic environment
000168371 260__ $$c2025
000168371 5060_ $$aAccess copy available to the general public$$fUnrestricted
000168371 5203_ $$aMelatonin is a key molecule in supporting pregnancy success in sheep, particularly under suboptimal conditions. In humans, melatonin is also known for its antioxidant properties. In addition, it has recently been reported that melatonin differentially drives cell fate in normal vs altered trophoblast cells. Given that, we hypothesize that melatonin is a potential partner for trophoblasts to overcome a hypoxic environment during the early stage of pregnancy. Here, we explore the effect of melatonin on early trophoblast cell behavior and its potential mitigating effect in CoCl2-induced hypoxia. Cell functionality and autophagy modulation were studied on ovine primary trophoblast cells (oTCs) 24 h treated with 250 µM melatonin with/without 200 µM CoCl2. First, melatonin exerts its antioxidant effects by reducing H2O2 levels under hypoxic cellular conditions (P < 0.0001). CoCl2 suppressed cell proliferation and migration (P < 0.0001); however, melatonin supplementation partially restored oTCs functionality (P < 0.05). Melatonin-mediated cytoprotective effects are manifested even through the modulation of cell fate mechanisms, particularly autophagy and apoptosis. Increased protein expression of autophagic markers (BCLN1 and LC3BII/LC3BI ratio) in concomitance with a decreased phosphorylation of mTOR was observed in CoCl2-treated cells (P < 0.01), while a reduced rate of autophagy was detected following melatonin co-treatment (P < 0.01). Similarly, melatonin attenuates the CoCl2-induced increase in apoptosis when administered concurrently (5.5 vs 1.8%, P < 0.01). These findings suggest that melatonin promotes autophagy over apoptosis, indicating a shift toward cell survival mechanisms. In addition, melatonin enhances cell functionality under hypoxia, suggesting the conceptus benefits from melatonin, particularly when it is forced to grow in a suboptimal environment.
000168371 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000168371 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000168371 700__ $$aAccornero, Paolo
000168371 700__ $$aQuarati, Elisa
000168371 700__ $$aManenti, Isabella
000168371 700__ $$aMiretti, Silvia
000168371 700__ $$aCanto, Francisco
000168371 700__ $$0(orcid)0000-0003-2827-3054$$aAbecia, José Alfonso$$uUniversidad de Zaragoza
000168371 700__ $$aToschi, Paola
000168371 7102_ $$12008$$2700$$aUniversidad de Zaragoza$$bDpto. Produc.Animal Cienc.Ali.$$cÁrea Producción Animal
000168371 773__ $$g6, 4 (2025), e250084 [12 pp.]$$tReproduction & fertility$$x2633-8386
000168371 8564_ $$s725273$$uhttps://zaguan.unizar.es/record/168371/files/texto_completo.pdf$$yVersión publicada
000168371 8564_ $$s1294111$$uhttps://zaguan.unizar.es/record/168371/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000168371 909CO $$ooai:zaguan.unizar.es:168371$$particulos$$pdriver
000168371 951__ $$a2026-02-04-13:14:42
000168371 980__ $$aARTICLE