Pregnancy-related changes in rat cervical glycosaminoglycans.
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ABSTRACT:
SUBMITTER: Golichowski AM
PROVIDER: S-EPMC1162301 | biostudies-other | 1980 Oct
REPOSITORIES: biostudies-other
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Project description:Aim: To identify pregnancy-associated changes in cervical noncoding RNA (ncRNA), including miRNA and long noncoding RNA (lncRNA), and their potential effects on biologic processes. Materials & methods: We enrolled 21 pregnant women with term deliveries (?37 weeks' gestation) in a prospective cohort and collected cervical swabs before 28 weeks' gestation. We enrolled 21 nonpregnant controls. We analyzed miRNA, lncRNA and mRNA expression, applying a Bonferroni correction. Results: Five miRNA and three lncRNA were significantly differentially (>twofold change) expressed. Putative miRNA targets are enriched in genes mediating organogenesis, glucocorticoid signaling, cell adhesion and ncRNA machinery. Conclusion: Differential cervical ncRNA expression occurs in the setting of pregnancy. Gene ontology classification reveals biological pathways through which miRNA may play a biologic role in normal pregnancy physiology.
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Project description:Glycosaminoglycans (GAGs) are essential components of the extracellular matrix, the natural environment from which cell behavior is regulated by a number or tissue homeostasis guarantors including growth factors. Because most heparin-binding growth factor activities are regulated by GAGs, structural and functional alterations of these polysaccharides may consequently affect the integrity of tissues during critical physiological and pathological processes. Here, we investigated whether the aging process can induce changes in the myocardial GAG composition in rats and whether these changes can affect the activities of particular heparin-binding growth factors known to sustain cardiac tissue integrity. Our results showed an age-dependent increase of GAG levels in the left ventricle. Biochemical and immunohistological studies pointed out heparan sulfates (HS) as the GAG species that increased with age. ELISA-based competition assays showed altered capacities of the aged myocardial GAGs to bind FGF-1, FGF-2, and VEGF but not HB EGF. Mitogenic assays in cultured cells showed an age-dependent decrease of the elderly GAG capacities to potentiate FGF-2 whereas the potentiating effect on VEGF(165) was increased, as confirmed by augmented angiogenic cell proliferation in Matrigel plugs. Moreover, HS disaccharide analysis showed considerably altered 6-O-sulfation with modest changes in N- and 2-O-sulfations. Together, these findings suggest a physiological significance of HS structural and functional alterations during aging. This can be associated with an age-dependent decline of the extracellular matrix capacity to efficiently modulate not only the activity of resident or therapeutic growth factors but also the homing of resident or therapeutic cells.
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Project description:Glycosaminoglycans (GAG) have diverse functions that regulate macromolecular assembly in the extracellular matrix. During pregnancy, the rigid cervix transforms to a pliable structure to allow birth. Quantitative assessment of cervical GAG is a prerequisite to identify GAG functions in term and preterm birth. In the current study, total GAG levels increased at term, yet the abundance, chain length, and sulfation levels of sulfated GAG remained constant. The increase in total GAG resulted exclusively from an increase in hyaluronan (HA). HA can form large structures that promote increased viscosity, hydration, and matrix disorganization as well as small structures that have roles in inflammation. HA levels increased from 19% of total GAG in early pregnancy to 71% at term. Activity of the HA-metabolizing enzyme, hyaluronidase, increased in labor, resulting in metabolism of large to small HA. Similar to mice, HA transitions from high to low molecular weight in term human cervix. Mouse preterm models were also characterized by an increase in HA resulting from differential expression of the HA synthase (Has) genes, with increased Has1 in preterm in contrast to Has2 induction at term. The Has2 gene but not Has1 is regulated in part by estrogen. These studies identify a shift in sulfated GAG dominance in the early pregnant cervix to HA dominance in term and preterm ripening. Increased HA synthesis along with hyaluronidase-induced changes in HA size in mice and women suggest diverse contributions of HA to macromolecular changes in the extracellular matrix, resulting in loss of tensile strength during parturition.
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Project description:Alterations in GABA(A) receptor (GABA(A)R) expression and function, similar to those we described previously during pregnancy in the mouse dentate gyrus, may also occur in other brain regions. Here we show, using immunohistochemical techniques, a decreased delta subunit-containing GABA(A)R (deltaGABA(A)R) expression in the dentate gyrus, hippocampal CA1 region, thalamus, and striatum but not in the cerebral cortex. In the face of the highly elevated neurosteroid levels during pregnancy, which can act on deltaGABA(A)Rs, it may be beneficial to decrease the number of neurosteroid-sensitive receptors to maintain a steady-state level of neuronal excitability throughout pregnancy. Consistent with this hypothesis, the synaptic input/output (I/O) relationship in the dentate gyrus molecular layer in response to lateral perforant path stimulation was shifted to the left in hippocampal slices from pregnant compared with virgin mice. The addition of allopregnanolone, at levels comparable with those found during pregnancy (100 nM), shifted the I/O curves in pregnant mice back to virgin levels. There was a decreased threshold to induce epileptiform local field potentials in slices from pregnant mice compared with virgin, but allopregnanolone reverted the threshold for inducing epileptiform activity to virgin levels. According to these data, neuronal excitability is increased in pregnant mice in the absence of allopregnanolone attributable to brain region-specific downregulation of deltaGABA(A)R expression. In brain regions, such as the cortex, that do not exhibit alterations in deltaGABA(A)R expression, there were no changes in the I/O relationship during pregnancy. Similarly, no changes in network excitability were detected in pregnant Gabrd(-/-) mice that lack deltaGABA(A)Rs, suggesting that changes in neuronal excitability during pregnancy are attributable to alterations in the expression of these receptors. Our findings indicate that alterations in deltaGABA(A)R expression during pregnancy result in brain region-specific increases in neuronal excitability that are restored by the high levels of allopregnanolone under normal conditions but under pathological conditions may result in neurological and psychiatric disorders associated with pregnancy and postpartum.
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Project description:Dysregulated remodeling of the cervix precedes preterm birth, a major cause of infant mortality and morbidity. The goal of this work was to identify changes in the mechanical properties of the cervix in late gestation. The tensile and load relaxation properties of cervices from rats 15-21 days (full term) post-conception were measured. Stiffness and load at 25% circumferential strain decreased with gestational age and correlated with the initial circumference of the cervix. Load-relaxation curves were accurately described by a seven parameter quasi-linear viscoelastic model, where three parameters associated with stiffness and load capacity decrease with gestational age and correlate with initial circumference. Time-dependent parameters did not depend on age or structure. Mechanical properties correlated with water content, but unexpectedly not with measures of collagen content, solubility, or organization. Quantitative measurements of cervical stiffness and structure will lead to a more accurate description of cervical remodeling and prediction of preterm birth.
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Project description:The aim of the present study was to dynamically observe and discuss the significance of inflammatory cytokines in cervical degenerative disease induced by unbalanced dynamic and static forces in rats. A total of 60 Sprague Dawley rats were randomized into test (n=45) and control (n=15) groups, which were randomly subdivided into three groups corresponding to assessment at one, three and six months post-operation. The test group included 10, 15 and 20 rats at the corresponding post-operative stage and the control group had five rats at each time-point. By excising cervicodorsal muscles and ligaments, an unbalanced dynamic and static rat model was established in the test group. At one, three and six-months post-operation, venous serum of test and control group rats was collected and inflammatory cytokines in the serum of all rats were quantitatively determined by ELISA. The results revealed that compared with the control group, the interleukin (IL)-1?, IL-10 and tumor necrosis factor-? levels in the test group were significantly increased at one and three months (P<0.05, <0.01 or <0.001), and that IL-12 was significantly increased at three months (P<0.05). However, transforming growth factor-?1 increased at one month but was significantly decreased at three months (P<0.01). IL-6 did not change significantly throughout the observation period (P>0.05). In conclusion, cervical vertebral stability may be accompanied with changes of inflammatory cytokines.
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Project description:Study Design Retrospective cohort study. Objective To compare sagittal cervical range of motion (ROM) and alignment in young versus middle-aged adults. Methods One hundred four asymptomatic adults were selected randomly out of 791 subjects who underwent lateral cervical radiographs in neutral, flexion, and extension positions. They were divided into two groups: young (age 20 to 29, 52 people) and middle-aged adults (age 50 to 59, 52 people). We determined the ROMs of upper cervical (occipital-C2 angle), midcervical (C2-C7 angle), and cervicothoracic spine (cervicosternal angle). We compared the alignment differences of the two groups by calculating the distances between C2 and C7 plumb lines, and C2 central-offset distance. Results In neutral position, there was no significant difference between young and middle-aged adults. However, in flexion, C2-C7 angle, distance between C2-C7 plumb lines, and C2 central-offset distance decreased with age. In extension, C2-C7 angle and C2 central-offset distance decreased with age. During flexion and extension, midcervical ROM and the range of C2 central-offset distance decreased in the middle-aged group. However, there was no difference between the two age groups in the ROM of the upper cervical and the cervicothoracic regions during flexion and extension. Conclusion We found that, despite of the presence of age-related cervical alignment changes, the only difference between the two groups was in the sagittal ROM of the midcervical spine during flexion and extension. Only the ROM of the midcervical spine appears to change significantly, consistent with findings that these levels are most likely to develop both symptomatic and asymptomatic degenerative changes.
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Project description: Not available
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