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Physiological reports
07, 2020;8 (13): e14476.

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

O'Llenecia S Walker, Rehginald Ragos, Harmeet Gurm, Mariah Lapierre, Linda L May, Sandeep Raha
Author Information
  1. O'Llenecia S Walker: Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
  2. Rehginald Ragos: Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
  3. Harmeet Gurm: Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
  4. Mariah Lapierre: Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
  5. Linda L May: Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
  6. Sandeep Raha: Department of Pediatrics, McMaster University, Hamilton, ON, Canada. ORCID
PMID: 32628362 DOI: 10.14814/phy2.14476

Abstract

The psychoactive component in cannabis, delta-9-tetrahydrocannabinol, can restrict fetal growth and development. Delta-9-tetrahydrocannabinol has been shown to negatively impact cellular proliferation and target organelles like the mitochondria resulting in reduced cellular respiration. In the placenta, mitochondrial dysfunction leading to oxidative stress prevents proper placental development and function. A key element of placental development is the proliferation and fusion of cytotrophoblasts to form the syncytium that comprises the materno-fetal interface. The impact of delta-9-tetrahydrocannabinol on this process is not well understood. To elucidate the nature of the mitochondrial dysfunction and its consequences on trophoblast fusion, we treated undifferentiated and differentiated BeWo human trophoblast cells, with 20 ��M delta-9-tetrahydrocannabinol for 48 hr. At this concentration, delta-9-tetrahydrocannabinol on BeWo cells reduced the expression of markers involved in syncytialization and mitochondrial dynamics, but had no effect on cell viability. Delta-9-tetrahydrocannabinol significantly attenuated the process of syncytialization and induced oxidative stress responses in BeWo cells. Importantly, delta-9-tetrahydrocannabinol also caused a reduction in the secretion of human chorionic gonadotropin and the production of human placental lactogen and insulin growth factor 2, three hormones known to be important in facilitating fetal growth. Furthermore, we also demonstrate that delta-9-tetrahydrocannabinol attenuated mitochondrial respiration, depleted adenosine triphosphate, and reduced mitochondrial membrane potential. These changes were also associated with an increase in cellular reactive oxygen species, and the expression of stress responsive chaperones, HSP60 and HSP70. These findings have important implications for understanding the role of delta-9-tetrahydrocannabinol-induced mitochondrial injury and the role this might play in compromising human pregnancies.

Keywords

cannabinoid mitochondria oxidative stress placenta trophoblasts

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Grants

  1. /CIHR

MeSH Term

Cannabinoid Receptor Agonists
Cell Line, Tumor
Cell Survival
Chaperonin 60
Dronabinol
Female
Giant Cells
Gonadotropins
HSP70 Heat-Shock Proteins
Humans
Insulin-Like Growth Factor II
Mitochondria
Mitochondrial Dynamics
Mitochondrial Proteins
Oxidative Stress
Trophoblasts

Chemicals

Cannabinoid Receptor Agonists
Chaperonin 60
Gonadotropins
HSP70 Heat-Shock Proteins
HSPD1 protein, human
Mitochondrial Proteins
Insulin-Like Growth Factor II
Dronabinol
Journal Article Research Support, Non-U.S. Gov't

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