Delta‐9‐tetrahydrocannabinol disrupts mitochondrial function and attenuates syncytialization in human placental BeWo cells

Walker, O’Llenecia S.; Ragos, Rehginald; Gurm, Harmeet; Lapierre, Mariah; May, Linda; Raha, Sandeep

doi:10.14814/phy2.14476

Cited by 28 publications

(41 citation statements)

References 91 publications

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“…Interestingly, inhibition of CB2 receptor did not significantly impact the effects of THC on the markers of mitochondrial fragmentation. We have made similar observations in syncytialized BeWo cells treated with THC 26 . Drawing from the “double-hit” hypothesis 80 in the context of trophoblast physiology, THC users may have compromised mitochondrial function such that they will less effectively handle the impact of a subsequent stressor on the mitochondrial reticulum (such as poor maternal nutritional status) 80 .…”

Section: Discussionsupporting

confidence: 80%

“…Mitochondrial morphology is determined by a dynamic equilibrium between organelle fusion and fission 52 . Perturbation of mitochondrial dynamics, as demonstrated by alterations in the transcriptional markers used in this study, has been linked to altered trophoblast function 26 , 30 , 41 . Importantly, increases in mitochondrial fission have been associated with poor gestational outcomes 31 .…”

Section: Discussionmentioning

confidence: 81%

“…Importantly, we have previously shown that THC impairs cytotrophoblast fusion into syncytia, hormonal secretion, and mitochondrial function, i.e. reduced ATP production and increased ROS production 26 .…”

Section: Discussionmentioning

confidence: 98%

“…Importantly, increases in mitochondrial fission have been associated with poor gestational outcomes 31 . Our previous study using human placental BeWo cells 26 demonstrated that THC treatment increased markers of mitochondrial fission and negatively impacted the secretion of hormones critical for fetal growth.…”

Section: Discussionmentioning

confidence: 99%

“…While there are presently no reported teratogenic effects, cannabis has been heavily implicated in neurodevelopmental disorders in the offspring 15 – 17 , intrauterine growth restriction 18 , 19 , and preterm birth 19 – 21 . Though the pathology and the mechanism(s) underpinning the adverse fetal outcomes associated with maternal cannabis use during pregnancy have yet to be fully elucidated, they are thought to stem from trophoblast abnormalities 22 – 26 .…”

Section: Introductionmentioning

confidence: 99%

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Delta-9-tetrahydrocannabinol inhibits invasion of HTR8/SVneo human extravillous trophoblast cells and negatively impacts mitochondrial function

Walker

Gurm

Sharma

et al. 2021

Sci Rep

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Prenatal cannabis use is a significant problem and poses important health risks for the developing fetus. The molecular mechanisms underlying these changes are not fully elucidated but are thought to be attributed to delta-9-tetrahydrocannabinol (THC), the main bioactive constituent of cannabis. It has been reported that THC may target the mitochondria in several tissue types, including placental tissue and trophoblast cell lines, and alter their function. In the present study, in response to 48-h THC treatment of the human extravillous trophoblast cell line HTR8/SVneo, we demonstrate that cell proliferation and invasion are significantly reduced. We further demonstrate THC-treatment elevated levels of cellular reactive oxygen species and markers of lipid damage. This was accompanied by evidence of increased mitochondrial fission. We also observed increased expression of cellular stress markers, HSP70 and HSP60, following exposure to THC. These effects were coincident with reduced mitochondrial respiratory function and a decrease in mitochondrial membrane potential. Taken together, our results suggest that THC can induce mitochondrial dysfunction and reduce trophoblast invasion; outcomes that have been previously linked to poor placentation. We also demonstrate that these changes in HTR8/SVneo biology may be variably mediated by cannabinoid receptors CB1 and CB2.

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Section: Discussionsupporting

confidence: 80%