TY - JOUR
T1 - First evidence of the protective role of melatonin in counteracting cadmium toxicity in the rat ovary via the mTOR pathway
AU - Kechiche, Safa
AU - Venditti, Massimo
AU - Knani, Latifa
AU - Jabłońska, Karolina
AU - Dzięgiel, Piotr
AU - Messaoudi, Imed
AU - Reiter, Russel J.
AU - Minucci, Sergio
N1 - Funding Information:
This study was supported by: Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University , Wroclaw, Poland; Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate “F. Bottazzi”, Università della Campania “Luigi Vanvitelli”, Napoli, Italy and Ministry of Higher Education, Scientific Research and Technology of Tunisia. The funding sources were not involved in the design of the study, or collection and analysis of data.
Funding Information:
This study was supported by: Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, Wroclaw, Poland; Dipartimento di Medicina Sperimentale, Sez. Fisiologia Umana e Funzioni Biologiche Integrate ?F. Bottazzi?, Universit? della Campania ?Luigi Vanvitelli?, Napoli, Italy and Ministry of Higher Education, Scientific Research and Technology of Tunisia. The funding sources were not involved in the design of the study, or collection and analysis of data.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Herein, the first evidence of the ability of melatonin (MLT) to counteract cadmium (Cd) toxic effects on the rat ovary is reported. Cd treatment, enhancing oxidative stress, provoked clear morphological, histological and biomolecular alterations, i.e. in the estrous cycle duration, in the ovarian and serum E2 concentration other than in the steroidogenic and folliculogenic genes expression. Results demonstrated that the use of MLT, in combination with Cd, avoided the changes, strongly suggesting that it is an efficient antioxidant for preventing oxidative stress in the rat ovary. Moreover, to explore the underlying mechanism involved, at molecular level, in the effects of Cd-MLT interaction, the study focused on the mTOR and ERK1/2 pathways. Interestingly, data showed that Cd influenced the phosphorylation status of mTOR, of its downstream effectors and of ERK1/2, inducing autophagy and apoptosis, while cotreatment with MLT nullified these changes. This work highlights the beneficial role exerted by MLT in preventing Cd-induced toxicity in the rat ovary, encouraging further studies to confirm its action on human ovarian health with the aim to use this indolamine to ameliorate oocyte quality in women with fertility disorders.
AB - Herein, the first evidence of the ability of melatonin (MLT) to counteract cadmium (Cd) toxic effects on the rat ovary is reported. Cd treatment, enhancing oxidative stress, provoked clear morphological, histological and biomolecular alterations, i.e. in the estrous cycle duration, in the ovarian and serum E2 concentration other than in the steroidogenic and folliculogenic genes expression. Results demonstrated that the use of MLT, in combination with Cd, avoided the changes, strongly suggesting that it is an efficient antioxidant for preventing oxidative stress in the rat ovary. Moreover, to explore the underlying mechanism involved, at molecular level, in the effects of Cd-MLT interaction, the study focused on the mTOR and ERK1/2 pathways. Interestingly, data showed that Cd influenced the phosphorylation status of mTOR, of its downstream effectors and of ERK1/2, inducing autophagy and apoptosis, while cotreatment with MLT nullified these changes. This work highlights the beneficial role exerted by MLT in preventing Cd-induced toxicity in the rat ovary, encouraging further studies to confirm its action on human ovarian health with the aim to use this indolamine to ameliorate oocyte quality in women with fertility disorders.
KW - Autophagy
KW - Cadmium toxicity
KW - Endocrine disruptor
KW - Melatonin
KW - Oxidative stress
KW - mTOR pathway
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U2 - 10.1016/j.envpol.2020.116056
DO - 10.1016/j.envpol.2020.116056
M3 - Article
C2 - 33199064
AN - SCOPUS:85096159501
VL - 270
JO - Environmental Pollution
JF - Environmental Pollution
SN - 0269-7491
M1 - 116056
ER -