title: Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites.
abstract: Maternal nutrition is an important determinant of one-carbon metabolism and defects in the one-carbon metabolism may lead to poor obstetric outcomes. This study was designed to test the hypothesis that altered intake/metabolism of micronutrients (folic acid and vitamin B12) and docosahexaenoic acid (DHA) contributes to increased homocysteine and oxidative stress leading to altered levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in women delivering preterm. We have earlier reported increased vitamin B12, homocysteine, and oxidative stress along with reduced placental DHA in women delivering preterm. In this study, we further examine the placental levels of MMP2, MMP3, TIMP1, and TIMP2 in 75 women delivering at term and 73 women delivering preterm. Placental levels of MMPs and TIMPs were determined by ELISA. Placental MMP2 and MMP3 levels were higher (P<0.01) in women delivering preterm as compared with term. There was no difference in the placental TIMP1 and TIMP2 levels in women delivering preterm and at term. Further placental MMP2 and MMP3 levels were higher (P<0.01) in women with preterm labor as compared with those in labor at term, suggesting that MMPs may favor degradation of extracellular matrix in the placenta during preterm labor. Our study for the first time suggests a crucial role of micronutrients and MMPs in preterm birth. Future studies need to examine if epigenetic modifications through the one-carbon cycle contribute to increased levels of MMPs leading to preterm deliveries.
authors: Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune 411043, India.
authors: Deepali
authors: D
authors: Sundrani
authors: Preeti
authors: P
authors: Chavan-Gautam
authors: Hemlata
authors: H
authors: Pisal
authors: Savita
authors: S
authors: Mehendale
authors: Sadhana
authors: S
authors: Joshi
mesh_terms: D000328:Adult; D002244:Carbon / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D018384:Oxidative Stress; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D047928:Premature Birth / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D004281:Docosahexaenoic Acids; D002244:Carbon; D053505:Matrix Metalloproteinases, Secreted; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2