title: Steroid Hormones Are Key Modulators of Tissue Mechanical Function via Regulation of Collagen and Elastic Fibers.
abstract: The extracellular matrix (ECM) plays an active and dynamic role that both reflects and facilitates the functional requirements of a tissue. The mature ECM of the nonpregnant cervix is drastically reorganized during pregnancy to drive changes in tissue mechanics that ensure safe birth. In this study, our research on mice deficient in the proteoglycan decorin have led to the finding that progesterone and estrogen play distinct and complementary roles to orchestrate structural reorganization of both collagen and elastic fibers in the cervix during pregnancy. Abnormalities in collagen and elastic fiber structure and tissue mechanical function evident in the cervix of nonpregnant and early pregnant decorin-null mice transiently recover for the remainder of pregnancy only to return 1 month postpartum. Consistent with the hypothesis that pregnancy levels of progesterone and estrogen may regulate ECM organization and turnover, expressions of factors required for assembly and synthesis of collagen and elastic fibers are temporally regulated, and the ultrastructure of collagen fibrils and elastic fibers is markedly altered during pregnancy in wild-type mice. Finally, utilizing ovariectomized nonpregnant decorin-null mice, we demonstrate structural resolution of collagen and elastic fibers by progesterone or estrogen, respectively, and the potential for both ECM proteins to contribute to mechanical function. These investigations advance understanding of regulatory factors that drive specialized ECM organization and contribute to an understanding of the cervical remodeling process, which may provide insight into potential complications associated with preterm birth that impact 9.6% of live births in the United States.
authors.affiliation: Department of Obstetrics and Gynecology and.|Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Shanmugasundaram
authors.initials: S
authors.lastname: Nallasamy
authors.affiliation: Department of Mechanical Engineering, Columbia University, New York, New York 10027; and.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Obstetrics and Gynecology and.|Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Meredith
authors.initials: M
authors.lastname: Akins
authors.affiliation: Department of Mechanical Engineering, Columbia University, New York, New York 10027; and.
authors.forename: Kristin
authors.initials: K
authors.lastname: Myers
authors.affiliation: Department of Pathology, Anatomy, and Cell Biology.|Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
authors.forename: Renato
authors.initials: R
authors.lastname: Iozzo
authors.affiliation: Department of Obstetrics and Gynecology and.|Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390.
authors.forename: Mala
authors.initials: M
authors.lastname: Mahendroo
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D004547:Elastic Tissue / Q000187:drug effects* / Q000378:metabolism; D004549:Elastin / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D051379:Mice; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D013314:Stress, Mechanical
chemical_list: D004967:Estrogens; D016326:Extracellular Matrix Proteins; D011374:Progesterone; D003094:Collagen; D004549:Elastin