Delta-9-tetrahydrocannabinol disrupts mitochondrial function and attenuates syncytialization in human placental BeWo...

Area of Science:

• Reproductive biology
• Cell biology
• Toxicology

Background:

• Delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis, is known to restrict fetal growth.
• Mitochondrial dysfunction in the placenta can lead to oxidative stress, hindering placental development and function.
• The effect of THC on cytotrophoblast fusion, crucial for placental development, is not well understood.

Purpose of the Study:

• To investigate the impact of delta-9-tetrahydrocannabinol (THC) on human trophoblast cell fusion.
• To elucidate the mechanisms of mitochondrial dysfunction induced by THC in placental cells.
• To assess the consequences of THC exposure on key placental hormones and fetal growth factors.

Main Methods:

• BeWo human trophoblast cells were treated with 20 µM delta-9-tetrahydrocannabinol (THC) for 48 hours.
• Assessed expression of markers for syncytialization and mitochondrial dynamics.
• Measured cell viability, oxidative stress markers, hormone secretion, and mitochondrial function (respiration, ATP levels, membrane potential).

Main Results:

• THC exposure reduced markers of syncytialization and mitochondrial dynamics without affecting cell viability.
• THC significantly attenuated trophoblast fusion and induced oxidative stress.
• THC decreased secretion of human chorionic gonadotropin, human placental lactogen, and insulin growth factor 2.
• THC impaired mitochondrial respiration, depleted ATP, reduced mitochondrial membrane potential, and increased reactive oxygen species and stress chaperones (HSP60, HSP70).

Conclusions:

• Delta-9-tetrahydrocannabinol (THC) disrupts human trophoblast cell fusion and placental development by inducing mitochondrial dysfunction and oxidative stress.
• THC-induced placental cell injury compromises the production of essential fetal growth hormones.
• These findings highlight the potential risks of THC exposure during pregnancy, contributing to restricted fetal growth and compromised pregnancies.