TY - JOUR
T1 - Impact of PFOS on maternal and placental lipid metabolism and decreased placental vascularization in a murine model
AU - Cheng, Zheyu
AU - Wan, Hin Ting
AU - Chan, Wing Yee
AU - Lam, Thomas Ka Yam
AU - WONG, Chris Kong Chu
N1 - This work was supported by the Hong Kong Baptist University (RC-FNRA-IG-20-21-SCI-01 and RC-SFCRG-23-24-SCI-01) to C.K.C.W. Lipidomic analysis, and MALDI-MSI were carried out in the Advanced Life Sciences and Mass Spectrophotometry Laboratory, Central Research Facilities, Hong Kong Baptist University.
Publisher copyright:
© 2025 The Author(s). Published by Elsevier B.V.
PY - 2025/11/29
Y1 - 2025/11/29
N2 - Epidemiological studies link PFAS exposure to gestational hypertension and preeclampsia. PFOS disrupts nutrient transfer and induces oxidative stress, but its effects on placental vascularization remain unclear. This study investigated how PFOS affects maternal and placental lipid profiles and impairs placental angiogenesis. Pregnant mice were gavage with PFOS (0.3 or 3 μg/g/day) from GD 0.5–14.5 to assess effects on lipid metabolism and placental vascularization. Lipidomic analysis at GD 14.5 revealed significant, dose-dependent alterations in maternal plasma and placental lipid profiles, centered on glycerophospholipids; placental changes included increased lysophosphatidylcholines (LPC) and lysophosphatidylethanolamines (LPE), decreased lysobisphosphatidic acid (LBPA), and a reduced phosphatidylcholine (PC)/sphingomyelin (SM) ratio, likely altering membrane properties and impairing endothelial cell function. Mass spectrometry imaging of whole fetuses and placentas showed a gradient increase in PFOS accumulation from the maternal to fetal side, with high PFOS density in the placental labyrinth zone of the high-dose (H-PFOS) group. Transcriptomic analysis of placentas identified disrupted vascularization pathways in response to H-PFOS exposure. Immunohistochemistry using endothelial markers (CD31 and ILB4) revealed PFOS-induced vascular changes, including a significant reduction in blood vessel formation in the H-PFOS group. This impairment correlated with elevated oxidative DNA damage, as indicated by increased 8-OHdG levels detected by Western blotting, along with upregulation of Nrf2, a key antioxidant regulator. Protein expression levels of the endothelial markers and vascular endothelial growth factors were concurrently reduced. Overall, these findings indicate that PFOS impairs placental angiogenesis by disrupting glycerophospholipid metabolism and inducing oxidative stress, potentially harming fetal development.
AB - Epidemiological studies link PFAS exposure to gestational hypertension and preeclampsia. PFOS disrupts nutrient transfer and induces oxidative stress, but its effects on placental vascularization remain unclear. This study investigated how PFOS affects maternal and placental lipid profiles and impairs placental angiogenesis. Pregnant mice were gavage with PFOS (0.3 or 3 μg/g/day) from GD 0.5–14.5 to assess effects on lipid metabolism and placental vascularization. Lipidomic analysis at GD 14.5 revealed significant, dose-dependent alterations in maternal plasma and placental lipid profiles, centered on glycerophospholipids; placental changes included increased lysophosphatidylcholines (LPC) and lysophosphatidylethanolamines (LPE), decreased lysobisphosphatidic acid (LBPA), and a reduced phosphatidylcholine (PC)/sphingomyelin (SM) ratio, likely altering membrane properties and impairing endothelial cell function. Mass spectrometry imaging of whole fetuses and placentas showed a gradient increase in PFOS accumulation from the maternal to fetal side, with high PFOS density in the placental labyrinth zone of the high-dose (H-PFOS) group. Transcriptomic analysis of placentas identified disrupted vascularization pathways in response to H-PFOS exposure. Immunohistochemistry using endothelial markers (CD31 and ILB4) revealed PFOS-induced vascular changes, including a significant reduction in blood vessel formation in the H-PFOS group. This impairment correlated with elevated oxidative DNA damage, as indicated by increased 8-OHdG levels detected by Western blotting, along with upregulation of Nrf2, a key antioxidant regulator. Protein expression levels of the endothelial markers and vascular endothelial growth factors were concurrently reduced. Overall, these findings indicate that PFOS impairs placental angiogenesis by disrupting glycerophospholipid metabolism and inducing oxidative stress, potentially harming fetal development.
KW - Lipidomic
KW - NRF2
KW - VEGF
KW - Lysobisphosphatidic acid
KW - Glycerophospholipids
UR - http://www.scopus.com/inward/record.url?scp=105023148303&partnerID=8YFLogxK
U2 - 10.1016/j.jhazmat.2025.140636
DO - 10.1016/j.jhazmat.2025.140636
M3 - Journal article
SN - 0304-3894
VL - 501
JO - Journal of Hazardous Materials
JF - Journal of Hazardous Materials
M1 - 140636
ER -
