TY - JOUR
T1 - Steroid hormones are key modulators of tissue mechanical function via regulation of collagen and elastic fibers
AU - Nallasamy, Shanmugasundaram
AU - Yoshida, Kyoko
AU - Akins, Meredith
AU - Myers, Kristin
AU - Iozzo, Renato
AU - Mahendroo, Mala
N1 - Publisher Copyright:
© 2017 Endocrine Society.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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.
AB - 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.
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U2 - 10.1210/en.2016-1930
DO - 10.1210/en.2016-1930
M3 - Article
C2 - 28204185
AN - SCOPUS:85016726535
SN - 0013-7227
VL - 158
SP - 950
EP - 962
JO - Endocrinology
JF - Endocrinology
IS - 4
ER -