Cannabidiol disrupts apoptosis, autophagy and invasion processes of placental trophoblasts

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Alves, P (Author) Other; Amaral, C (Author) Other; Teixeira, N (Author) Other; Georgina Correia da Silva (Author) FFUP

Journal

Title: Archives of Toxicology

Vol. 95

Pages: 3393-3406

ISSN: 0340-5761

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-00V-77V

DOI: 10.1007/s00204-021-03122-z

Abstract (EN): Cannabidiol (CBD) is a constituent of Cannabis sativa without psychotropic activity, whose medical benefits have been recognised. However, little is known about the potential toxic effects of CBD on reproductive health. Placental development involves tightly controlled processes of cell proliferation, differentiation, apoptosis, autophagy and migration/invasion of trophoblast cells. Cannabis use by pregnant women has been increasing, mainly for the relief of nausea associated with the first trimester, which raises great concern. Regarding the crucial role of cytotrophoblast cells (CTs) and extravillous trophoblasts (EVTs) in placentation, the effects of CBD (1-10 mu M) were studied, using in vitro model systems BeWo and HTR-8/SVneo cell lines, respectively. CBD causes cell viability loss in a dose-dependent manner, disrupts cell cycle progression and induces apoptosis through the mitochondrial pathway, on both cell models. Moreover, CBD induces autophagy only in HTR-8/SVneo cells, being this process a promoter of apoptosis. Hypoxia-responsive genes HIF1A and SPP1 were also increased in CBD-treated HTR-8/SVneo cells suggesting a role for HIF-1 alpha in the apoptotic and autophagic processes. In addition, CBD was able to decrease HTR-8/SVneo cell migration. Therefore, CBD interferes with trophoblast turnover and placental remodelling, which can have a considerable impact on pregnancy outcome. Thus, from an in vitro perspective our study adds new evidence for the potential negative impact of cannabis use by pregnant women.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14