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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.
Zheyu et al. (Sat,) studied this question.