Publications by Gunvor Ekman-Ordeberg
BACKGROUND: Premature prelabor rupture of fetal membranes accounts for 30% of all premature birth... more BACKGROUND: Premature prelabor rupture of fetal membranes accounts for 30% of all premature births and is associated with detrimental long-term infant outcomes. Premature cervical remodeling, facilitated by matrix metalloproteinases, may trigger rupture at the zone of the fetal membranes overlying the cervix. The similarities and differences underlying cervical remodeling in premature prelabor rupture of fetal membranes and spontaneous preterm labor with intact membranes are unexplored. OBJECTIVES: We aimed to perform the first transcriptomic assessment of the preterm human cervix to identify differences between premature prelabor rupture of fetal membranes and preterm labor with intact membranes and to compare the enzymatic activities of matrix metalloproteinases-2 and-9 between premature prelabor rupture of fetal membranes and preterm labor with intact membranes. STUDY DESIGN: Cervical biopsies were collected following preterm labor with intact membranes (n ¼ 6) and premature prelabor rupture of fetal membranes (n ¼ 5). Biopsies were also collected from reference groups at term labor (n ¼ 12) or term not labor (n ¼ 5). The Illumina HT-12 version 4.0 BeadChips microarray was utilized, and a novel network graph approach determined the specificity of changes between premature prelabor rupture of fetal membranes and preterm labor with intact membranes. Quantitative reverse transcriptionepolymerase chain reaction and Western blotting confirmed the microarray findings.
Papers by Gunvor Ekman-Ordeberg
The Integrity of Cervical Collagen during Pregnancy and Labor
Gynecologic and Obstetric Investigation, 1985
The concentration of collagen in the human uterine cervix decreases during pregnancy. This change... more The concentration of collagen in the human uterine cervix decreases during pregnancy. This change contributes to the ripening process, which facilitates cervical dilatation during labor. It has been suggested that cervical collagen is partly degraded at term and after delivery. In order to evaluate this hypothesis we investigated the proportion of intact to degraded collagen after solubilization of about 86% of the collagen with pepsin in acetic acid. Total collagen was quantitated as hydroxyproline whereas intact collagen was estimated by SDS-gel electrophoresis. The proportion of intact collagen to total collagen did not change during pregnancy and delivery. Furthermore it was similar to that of intact standard collagen. Thus, even if the concentration of collagen is diminished during pregnancy as a result of increased collagenolytic activity, there is no indication of a qualitative change of the remaining collagen.
Acta Obstetricia et Gynecologica Scandinavica, 2018
IntroductionAnti‐secretory factor is a protein that regulates secretory and inflammatory processe... more IntroductionAnti‐secretory factor is a protein that regulates secretory and inflammatory processes and preterm birth is associated with inflammation. Therefore, our hypothesis was that anti‐secretory factor might play a role in immune reactivity and homeostasis during pregnancy.Material and methodsFollowing spontaneous onset of labor and preterm or term delivery, placenta biopsies were collected. The levels of anti‐secretory factor and markers of inflammation (CD68, CD163) and vascularization (CD34, smooth muscle actin) were analyzed by immunohistochemistry.ResultsThe 61 placental biopsies included 31 preterm (<37 weeks of gestation) and 30 term (37–41 weeks) samples. The preterm placentas exhibited lower levels of anti‐secretory factor (p = 0.008) and larger numbers of CD68‐positive cells (p < 0.001) compared to term. Preterm placentas had blood vessel of smaller diameter (p = 0.036) indicative of immaturity. The level of interleukin‐6 in cord blood was higher after very pret...
American journal of obstetrics and gynecology, 2017
Premature prelabor rupture of fetal membranes accounts for 30% of all premature births and is ass... more Premature prelabor rupture of fetal membranes accounts for 30% of all premature births and is associated with detrimental long-term infant outcomes. Premature cervical remodeling, facilitated by matrix metalloproteinases, may trigger rupture at the zone of the fetal membranes overlying the cervix. The similarities and differences underlying cervical remodeling in premature prelabor rupture of fetal membranes and spontaneous preterm labor with intact membranes are unexplored. We aimed to perform the first transcriptomic assessment of the preterm human cervix to identify differences between premature prelabor rupture of fetal membranes and preterm labor with intact membranes and to compare the enzymatic activities of matrix metalloproteinases-2 and -9 between premature prelabor rupture of fetal membranes and preterm labor with intact membranes. Cervical biopsies were collected following preterm labor with intact membranes (n = 6) and premature prelabor rupture of fetal membranes (n = ...
Collagen Expression in Human Preterm Cervix
W134 Negative Affect, Stress and Inflammatory Cytokines in Mothers of Preterm Infants in Comparison to Mothers of Infants Born at Term
International journal of gynaecology and obstetrics, Oct 1, 2012
Circulating Cathelicidin Antimicrobial Peptide LL-37 Levels in Mothers and Preterm and Term Newborn Infants
Circulating Cathelicidin Antimicrobial Peptide LL-37 Levels in Mothers and Preterm and Term Newbo... more Circulating Cathelicidin Antimicrobial Peptide LL-37 Levels in Mothers and Preterm and Term Newborn Infants.
Childhood Experience of Parental Separation Is Associated With Labor IL-6 in Maternal Serum
Reproductive Sciences, 2015
Childhood Experience of Parental Separation Is Associated With Labor IL-6 in Maternal Serum
Collagen Expression in Human Preterm Cervix
Reproductive sciences (Thousand Oaks, Calif.), Jan 25, 2015
Remodeling of the cervix occurs in advance of labor both at term and at preterm birth. Morphologi... more Remodeling of the cervix occurs in advance of labor both at term and at preterm birth. Morphological characteristics associated with remodeling in rodents were assessed in cervix biopsies from women at term (39 weeks' gestation) and preterm (<33 weeks' gestation). Collagen I and III messenger RNA and hydroxyproline concentrations declined in cervix biopsies from women in labor at term and preterm compared to that in the cervix from nonlaboring women. Extracellular collagen was more degraded in sections of cervix from women at term, based on optical density of picrosirius red stain, versus that in biopsies from nonpregnant women. However, collagen structure was unchanged in the cervix from women at preterm labor versus the nonpregnant group. As an indication of inflammation, cell nuclei density was decreased in cervix biopsies from pregnant women irrespective of labor compared to the nonpregnant group. Moreover, CD68-stained macrophages increased to an equivalent extent in...
Altered Balance in Pro-Inflammatory and Anti-Inflammatory Cytokines in Preterm Cervical Ripening
Altered Balance in Pro-Inflammatory and Anti-Inflammatory Cytokines in Preterm Cervical Ripening
Reproductive biology and endocrinology : RB&E, Jan 23, 2009
Treatment with prostaglandin(PG)-E2 is clinically efficient for cervical priming. The aim of this... more Treatment with prostaglandin(PG)-E2 is clinically efficient for cervical priming. The aim of this study was to evaluate the impact of PG-E2 on the expression of the progesterone (PR), androgen (AR) and glucocorticoid (GR) receptors in human uterine cervix in prolonged pregnancy. The study groups were postterm nulliparous women with unripe cervices undergoing cervical priming with PG-E2 before labor induction. Responders (n = 12) who delivered vaginally were compared with non-responders (n = 10), who underwent cesarean section due to failure to progress to the active phase of labor. Controls (n = 18) with vaginal partus at a normal gestational age served as a reference group. Cervical levels of PR-A and PR- B isoforms, AR and GR, serum levels of their ligands and sex hormone-binding globulin (SHBG) were quantified. The responder group displayed lower total PR-AB and AR protein levels as compared to non-responders, and lower PR-B and AR protein levels as compared to controls. In addit...
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1998
During pregnancy and involution, an extensive remodelling of the human cervical connective tissue... more During pregnancy and involution, an extensive remodelling of the human cervical connective tissue occurs. This cervical ripening is one of the most pronounced physiological remodelling processes known in human connective tissue. To investigate how the remodelling is accomplished, the levels of mRNA for collagen I and III, versican and three small proteoglycans, biglycan, decorin and fibromodulin, were evaluated using Northern blots at different stages of cervical ripening. In the corresponding biopsies the concentration of collagen and of small and large proteoglycans were determined. Ž. The role of transforming growth factor-b TGF-b as a mediator of the remodelling process was also investigated. The concentration of collagen decreased and 1 week before partus, 50% of the nonpregnant level was attained. No further decrease was noted after partus. The mRNA for collagen I and III did, however, not decrease in the term pregnant cervix 1 week before partus. Only 20-30% decrease during the final ripening just before partus was recorded. Neither did the mRNA levels of the small proteoglycans change significantly during the ripening, despite an almost 50% decrease in the concentration of the small proteoglycans. The message for versican was, however, 5-fold increased at partus and then gradually returned to nonpregnant levels within 4 days after delivery. These changes corresponded to similar changes in the concentration of the large proteoglycan. Thus, the remodelling of the cervical connective tissue is achieved by two different mechanisms, on one hand an increased turnover of collagen and the small proteoglycans, on the other a changed transcription followed by an increased production of versican. During the involution 2-to 3-fold increases in the messages for collagen I and III, and the small proteoglycans, biglycan and decorin, corresponded to increases in the concentration of the small proteoglycans and non-extractable collagen. The message for TGF-b was increased 2-fold immediately after delivery compared with the term pregnant state. Thus, TGF-b may be of importance for the reconstruction of the cervix, which starts immediately after partus. q 1998 Elsevier Science B.V.
Increased Postpartum Collagenolytic Activity in Cervical Connective Tissue from Women Treated with Prostaglandin E2
Gynecologic and Obstetric Investigation, 1983
Cervical biopsies obtained from 7 patients immediately following parturition induced by intracerv... more Cervical biopsies obtained from 7 patients immediately following parturition induced by intracervical application of 0.5 mg prostaglandin E2 (PGE2) in viscous gel were compared with similar biopsies from 11 spontaneously delivered women. A DNP-peptide hydrolytic activity (collagenase) was significantly increased in cervical tissue from the PGE2-induced patients compared with controls. In patients with prompt clinical response, the increase was nearly twofold. No differences were found in the concentrations of water, sulfated glycosaminoglycans, hyaluronic acid, hydroxyproline or leukocyte elastase. Thus, PGE2-induced cervical priming seems to be associated with an increased collagenolytic activity.
BJOG: An International Journal of Obstetrics and Gynaecology, 1992
The Impact on Labor Induction of Intracervically Applied PGE 2 -GEL, Related to Gestational age in Patients with an Unripe Cervix
Acta Obstetricia et Gynecologica Scandinavica, 1983
In 54 patients with an unripe cervix in late third trimester, in which gestational age had been p... more In 54 patients with an unripe cervix in late third trimester, in which gestational age had been properly determined by repeated ultrasound scannings, labor was induced by intracervical application of 0.5 mg PGE2 in viscous gel. It was found that the outcome of the induced labor was not related to the gestational duration, but to the pre-inductive cervical score. Thus, the number of successful inductions was smaller and induction-delivery time longer, the lower the cervical score. Moreover, instrumental deliveries occurred most frequently in nulliparous women, with a low pre-inductive cervical score. Taking into consideration the difficulties of labor induction in the present type of patient, the overall proportion of instrumental deliveries (17%, including 7% cesarean sections) was low. No maternal or fetal side effects were observed. It is concluded that intracervical application a small dose of PGE2 in gel can be recommended for cervical priming and labor induction in pre- and post-term pregnancy.
Gene Expression Pattern in Cervix during Spontaneous Preterm Labor
Reproductive Sciences
Facts, views & vision in ObGyn, 2012
Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. Despite the current... more Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. Despite the current treatment procedures, the incidence of PTB has not changed in the past thirty years. Incomplete understanding of the biological and patophysiological mechanisms underlying preterm delivery is the major obstacle to prevent PTB. Cervical ripening is necessary for vaginal delivery and understanding of preterm cervical ripening is required for developing new treatment strategies. Several important substances such as HMGB1 and its receptors, CRH and its receptors and numerous cytokines are localized in the cervix and undergo distinct changes in labour. Other important -molecules, such as CRH, CRH-BP, CRH-R1, CRH-R2, HMGB1, TLR2, TLR4, IL-10, IL-12, are localized in the cervical epithelium, also indicating their role in the process of cervical ripening during labour. Furthermore, CRH stimulates IL-8 secretion from both preterm and term cervical fibroblasts. Recent studies from our group show ...
Reproductive biology and endocrinology : RB&E, 2006
The uterus is exposed to changes such as enlargement and distension during pregnancy and labor. I... more The uterus is exposed to changes such as enlargement and distension during pregnancy and labor. In these processes and in the process of cervical ripening, proprioceptive information is likely to be of great importance. Therefore, we wanted to study the possible existence of sensory nerve corpuscles in uterine corpus and cervix during pregnancy and labor. Studies on this aspect have not previously been perfomed. Biopsies were taken from the upper edge of the hysterotomy during caesarean section at term (n = 8), in labor (n = 5) and from the corresponding area in the non-pregnant uterus after hysterectomy (n = 7). Cervical biopsies were obtained transvaginally from the anterior cervical lip. Serial cryostat sections were prepared for immunohistochemistry using polyclonal antibodies against nerve growth factor receptor p75, protein gene product 9.5 and S-100. Structures with the characteristics of sensory nerve corpuscles were observed in several specimens after staining for p75, PGP ...
Reproductive Biology and Endocrinology, 2010
Background: In order to unravel the interactions between the epithelium and the extra cellular ma... more Background: In order to unravel the interactions between the epithelium and the extra cellular matrix (ECM) in breast tissue progressing to cancer, it is necessary to understand the relevant interactions in healthy tissue under normal physiologic settings. Proteoglycans in the ECM play an important role in the signaling between the different tissue compartments. The proteoglycan decorin is abundant in the breast stroma. Decreased expression in breast cancer tissue is a sign of a poor tumor prognosis. The heparane sulphate proteoglycans syndecan-1 and syndecan-4 promote the integration of cellular adhesion and proliferation. The aim of this study was to investigate the gene expression and location of decorin, syndecan-1 and syndecan-4 in the healthy breast during the menstrual cycle.
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Publications by Gunvor Ekman-Ordeberg
Papers by Gunvor Ekman-Ordeberg