Martha Lappas1,2. 1. Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia. 2. Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Abstract
PROBLEM: Metallothioneins (MTs) play important roles in regulating oxidative stress, inflammation, and hormone signaling. These processes play a major role in labor at term and preterm. The aims of this study were to characterize (a) temporal- and labor-associated changes and (b) the effect of pro-inflammatory and pro-labor insults on the expression of MT1 isoforms, MT2A, MT3, and MT4 in fetal membranes and myometrium. METHOD OF STUDY: The expression of MTs was assessed in fetal membranes and myometrium from nonlaboring and laboring women at preterm and term by RT-qPCR. Tissue explants were used to assess the effect of pro-inflammatory cytokines and Toll-like receptor (TLR) ligands on the expression of MTs in fetal membranes and myometrium. RESULTS: In fetal membranes, the expression of MT1A, MT1E, MT1F, MT1X, and MT2A was higher at term compared with preterm. Preterm labor and preterm histological chorioamnionitis were associated with increased expression of MT1A, MT1G, MT1M, MT1X, MT2A, and MT3. Term labor was associated with increased expression of MT1A, MT1F, MT1X, MT2A, and MT3 in fetal membranes and expression of MT1A, MT1E, MT1F, MT1G, MT1M, MT1X, MT2A, and MT3 in myometrium. Pro-inflammatory cytokines and TLR ligands increased the expression of MT1A, MT1E, MT1F, MT1G, MT1H, MT1X, and MT2A in fetal membranes and myometrium. CONCLUSION: Temporal-, labor-, and infection-associated increases in MT1 isoforms, MT2A, and MT3 have been observed in fetal membranes and/or myometrium. Furthermore, pro-inflammatory cytokines and bacterial and viral products increased the expression of MT1 isoforms, MT2A, MT3, and MT4 mRNA expression in fetal membranes and myometrium.
PROBLEM: Metallothioneins (MTs) play important roles in regulating oxidative stress, inflammation, and hormone signaling. These processes play a major role in labor at term and preterm. The aims of this study were to characterize (a) temporal- and labor-associated changes and (b) the effect of pro-inflammatory and pro-labor insults on the expression of MT1 isoforms, MT2A, MT3, and MT4 in fetal membranes and myometrium. METHOD OF STUDY: The expression of MTs was assessed in fetal membranes and myometrium from nonlaboring and laboring women at preterm and term by RT-qPCR. Tissue explants were used to assess the effect of pro-inflammatory cytokines and Toll-like receptor (TLR) ligands on the expression of MTs in fetal membranes and myometrium. RESULTS: In fetal membranes, the expression of MT1A, MT1E, MT1F, MT1X, and MT2A was higher at term compared with preterm. Preterm labor and preterm histological chorioamnionitis were associated with increased expression of MT1A, MT1G, MT1M, MT1X, MT2A, and MT3. Term labor was associated with increased expression of MT1A, MT1F, MT1X, MT2A, and MT3 in fetal membranes and expression of MT1A, MT1E, MT1F, MT1G, MT1M, MT1X, MT2A, and MT3 in myometrium. Pro-inflammatory cytokines and TLR ligands increased the expression of MT1A, MT1E, MT1F, MT1G, MT1H, MT1X, and MT2A in fetal membranes and myometrium. CONCLUSION: Temporal-, labor-, and infection-associated increases in MT1 isoforms, MT2A, and MT3 have been observed in fetal membranes and/or myometrium. Furthermore, pro-inflammatory cytokines and bacterial and viral products increased the expression of MT1 isoforms, MT2A, MT3, and MT4 mRNA expression in fetal membranes and myometrium.
Authors: Tove Wikström; Sanna Abrahamsson; Johan Bengtsson-Palme; Joakim Ek; Pihla Kuusela; Elham Rekabdar; Peter Lindgren; Ulla-Britt Wennerholm; Bo Jacobsson; Lil Valentin; Henrik Hagberg Journal: Clin Transl Med Date: 2022-09