Ivermectin induces apoptosis of porcine trophectoderm and uterine luminal epithelial cells through loss of mitochondrial membrane potential, mitochondrial calcium ion overload, and reactive oxygen species generation

Jin Young Lee, Whasun Lim, Jiyeon Ham, Jinyoung Kim, Seungkwon You, Gwonhwa Song

Research output: Contribution to journalArticle

Abstract

Ivermectin is a pesticide that has been used for over 30 years in livestock. Although there are a number of studies on the therapeutic potential of ivermectin, little is known about the effects of the drug during the early stage of pregnancy. In this study, we investigated the detrimental effects of ivermectin on porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells. Ivermectin not only inhibited the proliferation of both cells via the regulation of cell cycle-associated genes, but also induced apoptosis in pTr and pLE cells. We also verified its effect on mitochondrial dysfunction as shown by loss of mitochondrial membrane potential, mitochondrial Ca2+ overload, and reactive oxygen species (ROS) generation in pTr and pLE cells. As a mechanistic approach, we evaluated ivermectin-mediated cell signaling interactions including PI3K, AKT and MAPK pathways. Overall, our results suggest that constant exposure to and accumulation of ivermectin may cause abnormal fetal morphogenesis and placentation during the early stages of pregnancy. Our results may further provide a comprehensive understanding of the detrimental effects of ivermectin during pregnancy and will contribute to the establishment of a complete safety profile for ivermectin and its association with environmental pollution and public health in humans and livestock.

Original languageEnglish
JournalPesticide Biochemistry and Physiology
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Ivermectin
Mitochondrial Membrane Potential
ivermectin
membrane potential
reactive oxygen species
Reactive Oxygen Species
epithelial cells
Swine
apoptosis
Epithelial Cells
Ions
Apoptosis
ions
Calcium
calcium
swine
pregnancy
Livestock
Pregnancy
livestock

Keywords

  • Apoptosis
  • Ivermectin
  • Pig
  • Trophoblast
  • Uterine luminal epithelium

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Health, Toxicology and Mutagenesis

Cite this

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title = "Ivermectin induces apoptosis of porcine trophectoderm and uterine luminal epithelial cells through loss of mitochondrial membrane potential, mitochondrial calcium ion overload, and reactive oxygen species generation",
abstract = "Ivermectin is a pesticide that has been used for over 30 years in livestock. Although there are a number of studies on the therapeutic potential of ivermectin, little is known about the effects of the drug during the early stage of pregnancy. In this study, we investigated the detrimental effects of ivermectin on porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells. Ivermectin not only inhibited the proliferation of both cells via the regulation of cell cycle-associated genes, but also induced apoptosis in pTr and pLE cells. We also verified its effect on mitochondrial dysfunction as shown by loss of mitochondrial membrane potential, mitochondrial Ca2+ overload, and reactive oxygen species (ROS) generation in pTr and pLE cells. As a mechanistic approach, we evaluated ivermectin-mediated cell signaling interactions including PI3K, AKT and MAPK pathways. Overall, our results suggest that constant exposure to and accumulation of ivermectin may cause abnormal fetal morphogenesis and placentation during the early stages of pregnancy. Our results may further provide a comprehensive understanding of the detrimental effects of ivermectin during pregnancy and will contribute to the establishment of a complete safety profile for ivermectin and its association with environmental pollution and public health in humans and livestock.",
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AU - Lee, Jin Young

AU - Lim, Whasun

AU - Ham, Jiyeon

AU - Kim, Jinyoung

AU - You, Seungkwon

AU - Song, Gwonhwa

PY - 2019/1/1

Y1 - 2019/1/1

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