TY - JOUR
T1 - Flufenoxuron disturbs early pregnancy in pigs via induction of cell death with ER-mitochondrial dysfunction
AU - Bae, Hyocheol
AU - You, Seungkwon
AU - Lim, Whasun
AU - Song, Gwonhwa
N1 - Funding Information:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (grant number: 2018R1C1B6009048, 2019R1A2C2089914).
Funding Information:
This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (grant number: 2018R1C1B6009048, 2019R1A2C2089914 ).
Publisher Copyright:
© 2020
PY - 2021/1/5
Y1 - 2021/1/5
N2 - The use of pesticides can result in unintended side effects, such as environmental pollution and animal diseases; in serious cases, it may cause abortion. Flufenoxuron is an inhibitor of chitin synthesis that is used widely as a pesticide on farmland. It is difficult to break down and therefore accumulates in the body, and has also been detected in breast milk. Moreover, the effects of flufenoxuron in pregnancy remain elusive. Therefore, we investigated the effects of flufenoxuron on early pregnancy. Our results suggested that flufenoxuron inhibits cell development and cell cycle progression in porcine trophectoderm (pTr) cell and porcine endometrial luminal epithelial (pLE) cell lines through the repression of signal transduction pathways. Flufenoxuron induced programmed cell death through DNA fragmentation and apoptotic signals. In addition, flufenoxuron induced ROS production, ER stress, and mitochondrial malfunction; consequently, the cytosolic and mitochondrial calcium levels were increased. Expression of proteins on the ER-mitochondrial axis was increased by flufenoxuron. Cell migration was decreased by flufenoxuron treatment between pLE and pTr cells. In addition, the expression of pregnancy-related genes was decreased flufenoxuron. Collectively, our results indicated that flufenoxuron may be harmful to livestock and women in the early stages of pregnancy.
AB - The use of pesticides can result in unintended side effects, such as environmental pollution and animal diseases; in serious cases, it may cause abortion. Flufenoxuron is an inhibitor of chitin synthesis that is used widely as a pesticide on farmland. It is difficult to break down and therefore accumulates in the body, and has also been detected in breast milk. Moreover, the effects of flufenoxuron in pregnancy remain elusive. Therefore, we investigated the effects of flufenoxuron on early pregnancy. Our results suggested that flufenoxuron inhibits cell development and cell cycle progression in porcine trophectoderm (pTr) cell and porcine endometrial luminal epithelial (pLE) cell lines through the repression of signal transduction pathways. Flufenoxuron induced programmed cell death through DNA fragmentation and apoptotic signals. In addition, flufenoxuron induced ROS production, ER stress, and mitochondrial malfunction; consequently, the cytosolic and mitochondrial calcium levels were increased. Expression of proteins on the ER-mitochondrial axis was increased by flufenoxuron. Cell migration was decreased by flufenoxuron treatment between pLE and pTr cells. In addition, the expression of pregnancy-related genes was decreased flufenoxuron. Collectively, our results indicated that flufenoxuron may be harmful to livestock and women in the early stages of pregnancy.
KW - Endometrial cells
KW - Flufenoxuron
KW - Insecticides
KW - Pregnancy
KW - Trophectoderm
UR - http://www.scopus.com/inward/record.url?scp=85087769350&partnerID=8YFLogxK
U2 - 10.1016/j.jhazmat.2020.122996
DO - 10.1016/j.jhazmat.2020.122996
M3 - Article
C2 - 32763671
AN - SCOPUS:85087769350
SN - 0304-3894
VL - 401
JO - Journal of hazardous materials
JF - Journal of hazardous materials
M1 - 122996
ER -
