The long-range goal is to define morphological, structural, and functional interactions among cells of the fetal membranes that contribute to the maintenance of the physical integrity of this tissue. Selected studies of this project are coordinated with those designed to define the ontogeny of interstitial pro-collagen synthesis/processing in amnion. An alternative approach to most previous studies is proposed; viz, an investigation of the region of the fetal membranes most prone to rupture, i.e., the membranes immediately over the internal cervical os (""""""""dependent"""""""" membranes) prior to membrane rupture. Focusing on the amnion, the cellular and structural changes that may be involved in spontaneous rupture during labor and those that may create greater vulnerability for premature rupture (PT-PROM) will be defined. The amnion is an important physical/physiological barrier. but in some pregnancies during labor, leukocytes migrate into and sometimes through the fetal membranes to accumulate in the amniotic fluid (AF). Yet, surprisingly little is known about this process, including the origin of the cells, and the route and mechanisms of transmigration. We propose 3 specific aims. The goal of Aim 1 is to define, by anatomical and morphological analyses, the changes in cells, cellular relationships, and collagen structure in the amnion of the dependent membranes during gestation by immunohistochemistry, electron microscopy, and confocal laser scanning microscopy applied to both conventional sections and whole tissue examined en face. The goal of Aim 2 is to conduct similar analyses of changes related to labor, and in pregnancies in which there is increased risk of premature rupture, viz., maternal smoking. The goal of Aim 3 is to define the origin of leukocytes with the fetal membranes and AF, the capacity of these cells to produce inflammatory cytokines, and the role of the amnion in providing the chemotactic signals that promote leukocyte migration. Leukocytes in AF and tissues from pregnancies with male fetuses will be analyzed for the Y chromosome by in situ hybridization. Chemotaxis assays will be conducted to define the capacity of amnion tissue and isolated cells to produce chemokines in response to relevant stimuli (IL-1, LPS, phagocytosis, cadmium, and hypoxia) and the ability of leukocytes to transmigrate amnion tissue under various conditions. The findings of these studies should provide important new information to clarify selected aspects of amnion function for which there are significant clinical implications.
| Mahendroo, Mala (2018) Cervical hyaluronan biology in pregnancy, parturition and preterm birth. Matrix Biol : |
| Mendelson, Carole R; Montalbano, Alina P; Gao, Lu (2017) Fetal-to-maternal signaling in the timing of birth. J Steroid Biochem Mol Biol 170:19-27 |
| Chen, Chien-Cheng; Montalbano, Alina P; Hussain, Imran et al. (2017) The transcriptional repressor GATAD2B mediates progesterone receptor suppression of myometrial contractile gene expression. J Biol Chem 292:12560-12576 |
| Chigusa, Yoshitsugu; Kishore, Annavarapu Hari; Mogami, Haruta et al. (2016) Nrf2 Activation Inhibits Effects of Thrombin in Human Amnion Cells and Thrombin-Induced Preterm Birth in Mice. J Clin Endocrinol Metab 101:2612-21 |
| Gao, Lu; Wang, Gang; Liu, Wei-Na et al. (2016) Reciprocal Feedback Between miR-181a and E2/ER? in Myometrium Enhances Inflammation Leading to Labor. J Clin Endocrinol Metab 101:3646-3656 |
| Jimenez, Patricia T; Mainigi, Monica A; Word, R Ann et al. (2016) miR-200 Regulates Endometrial Development During Early Pregnancy. Mol Endocrinol 30:977-87 |
| Eskiocak, Ugur; Ramesh, Vijayashree; Gill, Jennifer G et al. (2016) Synergistic effects of ion transporter and MAP kinase pathway inhibitors in melanoma. Nat Commun 7:12336 |
| Gao, Lu; Rabbitt, Elizabeth H; Condon, Jennifer C et al. (2015) Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition. J Clin Invest 125:2808-24 |
| Renthal, Nora E; Williams, Koriand'r C; Montalbano, Alina P et al. (2015) Molecular Regulation of Parturition: A Myometrial Perspective. Cold Spring Harb Perspect Med 5: |
| Mogami, Haruta; Keller, Patrick W; Shi, Haolin et al. (2014) Effect of thrombin on human amnion mesenchymal cells, mouse fetal membranes, and preterm birth. J Biol Chem 289:13295-307 |
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