Changes in the biochemical constituents and morphologic appearance of the human cervical stroma during pregnancy.

OBJECTIVE The cervix is the lower portion of the uterus. It is composed of fibrous tissue and its mechanical integrity is crucial for maintaining a healthy gestation. During normal pregnancy, the cervical extracellular matrix (ECM) remodels in preparation for labor. The objective of this study was to investigate the biochemical and morphological changes in cervical stroma associated with physiological remodeling during normal pregnancy. STUDY DESIGN Using human cervical tissue obtained from pregnant and non-pregnant patients, the ECM was analyzed for its biochemical constituents and histologic morphology. The ECM was assayed for hydration, collagen concentration, collagen solubility, total sulfated glycosaminoglycan concentration, and individual disaccharide concentration. The ECM morphology was visualized using conventional histological techniques (Masson's trichrome stain, polarized light microscopy) as well as second harmonic generation (SHG) imaging. RESULTS When comparing pregnant to non-pregnant tissue, significant increases were measured for total sulfated glycosaminoglycans, hyaluronic acid, and collagen solubility. The microscopy studies confirmed that the collagenous network of the cervical stroma was anisotropic and pregnancy was associated with a discernable decrease in collagen organization. CONCLUSION Significant changes were seen in the concentration and organization of cervical ECM constituents during normal pregnancy.

[1]  S. Socrate,et al.  Mechanical and biochemical properties of human cervical tissue. , 2008, Acta biomaterialia.

[2]  R. Aspden The theory of fibre-reinforced composite materials applied to changes in the mechanical properties of the cervix during pregnancy. , 1988, Journal of theoretical biology.

[3]  Y. Mori,et al.  The change in solubility of type I collagen in human uterine cervix in pregnancy at term. , 1979, Biochemical medicine.

[4]  M. Endo,et al.  Glycoconjugates (glycosaminoglycans and glycoproteins) and glycogen in the human cervix uteri. , 1980, The Tohoku journal of experimental medicine.

[5]  A Ratcliffe,et al.  Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis , 1994, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[6]  A. Plaas,et al.  Glycosaminoglycan Sulfation in Human Osteoarthritis , 1998, The Journal of Biological Chemistry.

[7]  D. Danforth,et al.  The effect of pregnancy and labor on the human cervix: changes in collagen, glycoproteins, and glycosaminoglycans. , 1974, American journal of obstetrics and gynecology.

[8]  H. Stegemann,et al.  Determination of hydroxyproline. , 1967, Clinica chimica acta; international journal of clinical chemistry.

[9]  Leslie M Loew,et al.  Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms , 2003, Nature Biotechnology.

[10]  S. S. Townsend,et al.  Phase Matching considerations in Second Harmonic Generation from tissues: Effects on emission directionality, conversion efficiency and observed morphology. , 2008, Optics communications.

[11]  R. Midura,et al.  Adaptation of FACE methodology for microanalysis of total hyaluronan and chondroitin sulfate composition from cartilage. , 2000, Glycobiology.

[12]  T Kobayashi,et al.  The role of hyaluronic acid as a mediator and regulator of cervical ripening. , 1997, Human reproduction.

[13]  K. Grande-Allen,et al.  Valve proteoglycan content and glycosaminoglycan fine structure are unique to microstructure, mechanical load and age: Relevance to an age-specific tissue-engineered heart valve. , 2008, Acta biomaterialia.

[14]  R. Midura,et al.  Fluorophore-assisted carbohydrate electrophoresis (FACE) of glycosaminoglycans. , 2001, Osteoarthritis and cartilage.

[15]  Peter Niederer,et al.  Three-dimensional fiber architecture of the nonpregnant human uterus determined ex vivo using magnetic resonance diffusion tensor imaging. , 2006, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[16]  E. Chien,et al.  Mifepristone-induced cervical ripening: structural, biomechanical, and molecular events. , 2006, American journal of obstetrics and gynecology.

[17]  E. A. Friedman,et al.  Computer analysis of labor progression. 3. Pattern variations by parity. , 1971, The Journal of reproductive medicine.

[18]  P. Leppert,et al.  Collagen Changes in Rat Cervix in Pregnancy—Polarized Light Microscopic and Electron Microscopic Studies , 1995, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[19]  E. Thonar,et al.  Altered Fine Structures of Corneal and Skeletal Keratan Sulfate and Chondroitin/Dermatan Sulfate in Macular Corneal Dystrophy* , 2001, The Journal of Biological Chemistry.

[20]  N. Uldbjerg,et al.  Ripening of the human uterine cervix related to changes in collagen, glycosaminoglycans, and collagenolytic activity. , 1983, American journal of obstetrics and gynecology.

[21]  H. J. Conn,et al.  Staining procedures used by the Biological Stain Commission. , 1974 .

[22]  Koichi Masuda,et al.  Tensile mechanical properties of bovine articular cartilage: Variations with growth and relationships to collagen network components , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[23]  R. Midura,et al.  Chemical and Immunological Assay of the Nonreducing Terminal Residues of Chondroitin Sulfate from Human Aggrecan* , 1997, The Journal of Biological Chemistry.

[24]  F. Wusteman The Methodology of Connective Tissue Research , 1976 .

[25]  F. Glorieux,et al.  Collagen changes in the human uterine cervix at parturition. , 1978, American journal of obstetrics and gynecology.

[26]  N. Uldbjerg,et al.  Connective Tissue Changes in the Cervix During Normal Pregnancy and Pregnancy Complicated by Cervical Incompetence , 1988, Obstetrics and gynecology.

[27]  R M Aspden,et al.  Collagen organisation in the cervix and its relation to mechanical function. , 1988, Collagen and related research.

[28]  N. Uldbjerg,et al.  Cervical collagen in non-pregnant women with previous cervical incompetence. , 1996, European journal of obstetrics, gynecology, and reproductive biology.

[29]  U Ulmsten,et al.  Changes in the connective tissue of corpus and cervix uteri during ripening and labour in term pregnancy , 1989, British journal of obstetrics and gynaecology.

[30]  T. Eskes The extracellular matrix of the uterus, cervix and fetal membranes: synthesis, degradation and hormonal regulation , 1992 .

[31]  D. A. Hall The Methodology of connective tissue research , 1976 .

[32]  B. Zimmermann,et al.  The solubility of collagen of the uterine cervix during pregnancy and labour , 1976, Archiv für Gynäkologie.

[33]  P. So,et al.  Single-Photon Counting Multicolor Multiphoton Fluorescence Microscope , 2005, Journal of Fluorescence.

[34]  G. Saade,et al.  Control and assessment of the uterus and cervix during pregnancy and labour. , 1998, Human reproduction update.

[35]  R W Farndale,et al.  A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. , 1982, Connective tissue research.