/manager/Index ${session.getAttribute("locale")} 5 Oxidative stress, placental ageing-related pathologies and adverse pregnancy outcomes /manager/Repository/uon:32096 Wed 09 Feb 2022 15:57:52 AEDT ]]> Is there a role for placental senescence in the genesis of obstetric complications and fetal growth restriction? /manager/Repository/uon:32076 Thu 27 Jan 2022 15:57:09 AEDT ]]> Inhibition of vertebrate aldehyde oxidase as a therapeutic treatment for cancer, obesity, aging and amyotrophic lateral sclerosis /manager/Repository/uon:40081 Thu 14 Jul 2022 11:54:12 AEST ]]> Evidence that fetal death is associated with placental aging /manager/Repository/uon:30931 41 completed weeks of gestation (late-term) would show changes consistent with aging that would also be present in placentas associated with stillbirths. Objective: We sought to determine whether placentas from late-term pregnancies and unexplained stillbirth show oxidative damage and other biochemical signs of aging. We also aimed to develop an in vitro term placental explant culture model to test the aging pathways. Study Design: We collected placentas from women at 37-39 weeks’ gestation (early-term and term), late-term, and with unexplained stillbirth. We used immunohistochemistry to compare the 3 groups for: DNA/RNA oxidation (8-hydroxy-deoxyguanosine), lysosomal distribution (lysosome-associated membrane protein 2), lipid oxidation (4-hydroxynonenal), and autophagosome size (microtubule-associated proteins 1A/1B light chain 3B, LC3B). The expression of aldehyde oxidase 1 was measured by real-time polymerase chain reaction. Using a placental explant culture model, we tested the hypothesis that aldehyde oxidase 1 mediates oxidative damage to lipids in the placenta. Results: Placentas from late-term pregnancies show increased aldehyde oxidase 1 expression, oxidation of DNA/RNA and lipid, perinuclear location of lysosomes, and larger autophagosomes compared to placentas from women delivered at 37-39 weeks. Stillbirth-associated placentas showed similar changes in oxidation of DNA/RNA and lipid, lysosomal location, and autophagosome size to placentas from late-term. Placental explants from term deliveries cultured in serum-free medium also showed evidence of oxidation of lipid, perinuclear lysosomes, and larger autophagosomes, changes that were blocked by the G-protein-coupled estrogen receptor 1 agonist G1, while the oxidation of lipid was blocked by the aldehyde oxidase 1 inhibitor raloxifene. Conclusion: Our data are consistent with a role for aldehyde oxidase 1 and G-protein-coupled estrogen receptor 1 in mediating aging of the placenta that may contribute to stillbirth. The placenta is a tractable model of aging in human tissue.]]> Thu 09 Dec 2021 11:03:44 AEDT ]]> Increased oxidative damage and premature placental aging contribute to the aetiology of stillbirth /manager/Repository/uon:33234 Mon 23 Sep 2019 11:54:38 AEST ]]>