Cannabis sativa tetrahydrocannabinol (THC) impact on placental endocrine function
L. Midão1,3,, , J. Maia1,2, M. Almada1,2, B. Fonseca1,2, D. Gonçalves4, J. Braga4, N. Teixeira1,2, G. Correia-da-Silva1,2
1 Laboratório de Bioquímica, Faculdade de Farmácia Universidade do Porto, Porto, Portugal
2 UCIBIO-REQUIMTE, Porto, Portugal
3 Departamento de Química, Universidade de Aveiro, Aveiro, Portugal
4 Departamento da Mulher e da Medicina Reprodutiva, Serviço de Obstetrícia, Centro Materno-Infantil do Norte- Centro Hospitalar do Porto, Porto, Portugal

Aim: The main goal of this work is to understand the impact of THC on placenta endocrine function.

Introduction: Cannabis sativa-based medicines have been used to help ease pain, nausea and loss of appetite in cancer and HIV patients. Endocannabinoid system plays an important role in the regulation of female fertility and pregnancy. This system is implicated in proliferation, differentiation and apoptosis of placental stem cells, the trophoblasts (1). These mediate critical steps such as hormone production, fetal immune protection and increase in maternal vascular blood flow. Previous studies have shown that cannabis consumption during pregnancy is associated with intrauterine growth restriction, preterm labor and low birth weight. Moreover, tetrahydrocannabinol (THC), the main psychoactive compound of cannabis, is able to cross the placental barrier. However its effect on trophoblasts turnover and hormone production are unknown.

Methods: Term placental explants were treated with THC [1–40μM] for 24h to 72h. The relative mRNA levels of 3β-HSD, aromatase, leptin and PP13 were determined by qRT-PCR. The protein expression levels of 3β-HSD, aromatase and leptin were assessed by Western Blot. Progesterone, estradiol and β-human chorionic gonadotropin (β-hCG) levels were measured by ELFA.

Results: After 24h, PP13 mRNA levels were significantly increased at 40μM of THC, while for leptin this effect was observed at 10μM. Moreover, after 72h aromatase mRNA levels were increased, while there was no effect on 3β-HSD. No differences were observed regarding progesterone whilst, an increase in estradiol and β-hCG with 40μM at 72h was detected.

Conclusion: These findings suggest that THC may impair trophoblast turnover and endocrine function which may affect pregnancy outcome. Moreover these results may contribute to disclose the cellular effects of cannabis-derived drugs.

Acknowledgements: Work financed by FEDER through COMPETE and FCT through PTDC/DTP-FTO/5651/2014-POCI-01-0145-FEDER-016562; FCT/MEC and FEDER, under PT2020 (UID/01/0145/FERDER/007728) and CCDR-N/NORTE2020/Portugal 2020 (norte-01-0145-FEDER-000024.1

M.A. Costa,B.M. Fonseca,N.A. Teixeira,G. Correia-da-Silva
The endocannabinoid anandamide induces apoptosis in cytotrophoblast cells: involvement of both mitochondrial and death receptor pathways
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