The psychoactive compound of Cannabis sativa, Delta(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

Costa, MA (Autor) Outra; Fonseca, BM (Autor) Outra; Franklim Marques (Autor) FFUP; Teixeira, NA (Autor) FFUP; Georgina Correia da Silva (Autor) FFUP

Revista

Título: Toxicology

Vol. 334

Páginas: 94-103

ISSN: 0300-483X

Editora: Elsevier

Indexação

ISI Web of Knowledge - 12 Citações

Scopus - 22 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-00G-D5H

DOI: 10.1016/j.tox.2015.06.005

Abstract (EN): The noxious effects of cannabis consumption for fertility and pregnancy outcome are recognized for years. Its consumption during gestation is associated with alterations in foetal growth, low birth weight and preterm labor. The main psychoactive molecule of cannabis, Delta(9)-tetrahydrocannabinol (THC) impairs the production of reproductive hormones and is also able to cross the placenta barrier. However, its effect on the main placental cells, the trophoblasts, are unknown. Actually, the role of THC in cell survival/death of primary human cytotrophoblasts (CTs) and syncytiotrophoblasts (STs) and in the syncytialization process remains to be explored. Here, we show that THC has a dual effect, enhancing MTT metabolism at low concentrations, whereas higher doses decreased cell viability, on both trophoblast phenotypes, though the effects on STs were more evident. THC also diminished the generation of oxidative and nitrative stress and the oxidized form of glutathione, whereas the reduced form of this tripeptide was increased, suggesting that THC prevents ST cell death due to an antioxidant effect. Moreover, this compound enhanced the mitochondrial function of STs, as observed by the increased MU metabolism and intracellular ATP levels. These effects were independent of cannabinoid receptors activation. Besides, THC impaired Cl' differentiation into STs, since it decreased the expression of biochemical and morphological biomarkers of syncytialization, through a cannabinoid receptor-dependent mechanism. Together, these results suggest that THC interferes with trophoblast turnover, preventing trophoblast cell death and differentiation, and contribute to disclose the cellular mechanisms that lead to pregnancy complications in women that consume cannabis-derived drugs during gestation.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10