TY - JOUR
T1 - Exposure to fipronil induces cell cycle arrest, DNA damage, and apoptosis in porcine trophectoderm and endometrial epithelium, leading to implantation defects during early pregnancy
AU - Park, Wonhyoung
AU - Lim, Whasun
AU - Song, Gwonhwa
N1 - Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number: 2020R1A6A3A13075810 ) and the National Research Foundation of Korea (NRF) grant funded by the Korea government ( MSIT ) (grant number: 2021R1A2C2005841 & 2021R1C1C1009807 ).
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/12/15
Y1 - 2021/12/15
N2 - Fipronil, a phenyl-pyrazole insecticide, has a wide range of uses, from agriculture to veterinary medicine. Due to its large-scale applications, the risk of environmental and occupational exposure and bioaccumulation raises concerns. Moreover, relatively little is known about the intracellular mechanisms of fipronil in trophoblasts and the endometrium involved in implantation. Here, we demonstrated that fipronil reduced the viability of porcine trophectoderm and luminal epithelial cells. Fipronil induced cell cycle arrest at the sub-G1 phase and apoptotic cell death through DNA fragmentation and inhibition of DNA replication. These reactions were accompanied by homeostatic changes, including mitochondrial depolarization and cytosolic calcium depletion. In addition, we found that exposure to fipronil compromised the migration and implantation ability of pTr and pLE cells. Moreover, alterations in PI3K-AKT and MAPK-ERK1/2 signal transduction were observed in fipronil-treated pTr and pLE cells. Finally, the antiproliferative and apoptotic effects of fipronil were also demonstrated in 3D cell culture conditions. In summary, our results suggest that fipronil impairs implantation potentials in fetal trophectoderm and maternal endometrial cells during early pregnancy.
AB - Fipronil, a phenyl-pyrazole insecticide, has a wide range of uses, from agriculture to veterinary medicine. Due to its large-scale applications, the risk of environmental and occupational exposure and bioaccumulation raises concerns. Moreover, relatively little is known about the intracellular mechanisms of fipronil in trophoblasts and the endometrium involved in implantation. Here, we demonstrated that fipronil reduced the viability of porcine trophectoderm and luminal epithelial cells. Fipronil induced cell cycle arrest at the sub-G1 phase and apoptotic cell death through DNA fragmentation and inhibition of DNA replication. These reactions were accompanied by homeostatic changes, including mitochondrial depolarization and cytosolic calcium depletion. In addition, we found that exposure to fipronil compromised the migration and implantation ability of pTr and pLE cells. Moreover, alterations in PI3K-AKT and MAPK-ERK1/2 signal transduction were observed in fipronil-treated pTr and pLE cells. Finally, the antiproliferative and apoptotic effects of fipronil were also demonstrated in 3D cell culture conditions. In summary, our results suggest that fipronil impairs implantation potentials in fetal trophectoderm and maternal endometrial cells during early pregnancy.
KW - Apoptosis
KW - Cytotoxicity
KW - Fipronil
KW - Implantation
KW - Trophectoderm
UR - http://www.scopus.com/inward/record.url?scp=85115933058&partnerID=8YFLogxK
U2 - 10.1016/j.envpol.2021.118234
DO - 10.1016/j.envpol.2021.118234
M3 - Article
C2 - 34582916
AN - SCOPUS:85115933058
VL - 291
JO - Environmental Pollution
JF - Environmental Pollution
SN - 0269-7491
M1 - 118234
ER -