319. RELAXIN REGULATES AQUAPORIN EXPRESSION IN THE CERVIX OF LATE PREGNANT MICE

2010 ◽  
Vol 22 (9) ◽  
pp. 119
Author(s):  
Y. Soh ◽  
L. J. Parry
Keyword(s):  
Fluid Balance ◽  
Late Pregnancy ◽  
Fold Increase ◽  
Peptide Hormone ◽  
Cervical Ripening ◽  
Aqp5 Expression ◽  
Pregnant Mice ◽  
Wet Weight ◽  
Circulating Levels ◽  
Relaxin Receptor

Aquaporins (AQPs) have been implicated in the regulation of fluid balance in the cervix during pregnancy to promote hydration, a characteristic of cervical ripening in late gestation.There are four AQPs in the cervix; AQP3, 4, 5 and 8. Cervical fluid balance involves AQP5 and 8 in early pregnancy and AQP3 and 4 in late pregnancy [1]. However, the factors involved in the regulation of cervical AQPs are unknown. We propose that the ovarian peptide hormone relaxin regulates cervical AQPs because high circulating levels of relaxin correspond to changes in AQPs and it is involved in cervical ripening. To test this hypothesis, expression of aqp3, 5 and 8 was compared in the cervices of relaxin wildtype (Rln+/+) and relaxin knockout (Rln–/–) at various stages of pregnancy (day 14.5, 16.5 and 18.5 pregnancy) by quantitative PCR. In the Rln–/– mice, aqp3 expression was significantly lower on day 18.5 gestation compared to Rln+/+ littermates. Aqp5 and 8 expression did not change significantly between genotypes. To determine whether relaxin could restore the Rln+/+ phenotype, Rln–/– mice were implanted with Alzet osmotic minipumps on day 12.5 pregnancy to infuse either recombinant H2 human relaxin (200 μg/mL; Corthera Inc) or 0.9% saline as a control. Cervices were collected after 4 or 6 days of infusion for gene expression analysis. Relaxin infusion in pregnant Rln–/– mice increased cervical aqp3, and also decreased aqp5 expression compared with saline-controls in the 6-day infusion group. Additionally, relaxin treatment caused a 6-fold increase in cervix wet weight, dispersal of collagen fibres and a decrease in relaxin receptor (Rxfp1) expression. These data suggest that relaxin promotes cervical hydration through an action on AQPs. (1) Anderson et al, 2006. Endocrinology 147(1): 130–140.

244. Effects of relaxin treatment on hyaluronic synthase expression in the cervix of pregnant relaxin-deficient (Rln-/-) mice

2008 ◽  
Vol 20 (9) ◽  
pp. 44
Author(s):  
Y. M. Soh ◽  
L. A. Vodstrcil ◽  
L. J. Parry
Keyword(s):  
Water Content ◽  
Collagen Fibre ◽  
Late Pregnancy ◽  
Fold Increase ◽  
Cervical Ripening ◽  
Water Molecules ◽  
Qpcr Analysis ◽  
Fibre Degradation ◽  
Wet Weight ◽  
Relaxin Receptor

The cervical extracellular matrix (ECM) changes extensively in a process called cervical ripening in late pregnancy. This occurs through a complex series of processes leading to collagen fibre degradation and dispersal. We tested the hypothesis that relaxin increases cervical water content by stimulating hyaluronic synthase (HAS) enzymes that regulate hyaluronic acid (HA) synthesis. HA is thought to recruit water molecules into interstitial spaces between collagen fibrils, causing them to disperse. In the first study, cervices were collected from Rln+/+ and Rln−/− mice on days 14.5, 16.5, 18.5 and 19 gestation, and day 1 postpartum (PP) to compare has expression between the genotypes by qPCR analysis. In the second study, Rln−/− mice were implanted with Alzet osmotic minipumps on day 12.5 gestation to infuse either recombinant H2 human relaxin (200 μg/mL; BAS Medical Inc.) or 0.9% saline at a continuous flow rate of 0.5 μl/h. Cervices were collected after 4 or 6 days of infusion. has1 and has2 gene expression increased significantly at term and decreased immediately postpartum in the Rln+/+ mice. Although has1 and has2 were expressed in Rln−/− mice, there was no increase in expression on day 18.5 gestation and cervix wet weight did not increase compared with Rln+/+ mice. Relaxin infusion for 4 or 6 days in pregnant Rln−/− mice significantly increased cervical has2 but decreased has1 expression compared with saline-controls. Additionally, relaxin treatment caused a 6-fold increase in cervix wet weight, a 5% increase in water content and a significant decrease in relaxin receptor (Rxfp1) expression compared with saline-controls. These data suggest that relaxin promotes cervical hydration through an has2-mediated increase in HA, and may facilitate cervical ripening by causing collagen fibril dispersal in the ECM.

Biochemical studies of intrauterine components of the tammar wallaby Macropus eugenii during pregnancy

Development ◽  
1981 ◽  
Vol 62 (1) ◽  
pp. 325-338
Author(s):  
Elizabeth J. Thornber ◽  
Marilyn B. Renfree ◽  
Gregory I. Wallace
Keyword(s):  
Protein Concentration ◽  
Specific Binding ◽  
Polyacrylamide Gel Electrophoresis ◽  
Fold Increase ◽  
Tammar Wallaby ◽  
Macropus Eugenii ◽  
Tenfold Increase ◽  
Specific Proteins ◽  
Wet Weight

The in vitro uptake and incorporation of [3H]ui idine by blastocysts of the tammar wallaby showed a 16- and 30-fold increase from day 0 to day 10 after removal of pouch young, respectively. Two of the six non-expanded blastocysts recovered on day 5 showed a tenfold increase in incorporation. During the first ten days after removal of pouch young the diameter of the blastocyst increased threefold. Endometrial exudate from gravid uteri had a higher protein concentration than exudate from nongravid uteri (39·5 ± 0·9 and 32·0 ± 2·0 mg/ml (mean ± s.e.m.), respectively). Endometrial exudates from uteri where the blastocyst was actively growing were found to contain six uterine-specific proteins. These were separated by gradient polyacrylamide gel electrophoresis. Two of the proteins were pre-albumins and the others were larger molecules (M.W. 153000–670000). Two proteins were only present at particular stages of pregnancy: the other four were present at all stages from diapause to birth, in exudate from gravid and nongravid uteri. The specific binding of progesterone and androstenedione to proteins in endometrial exudates or uterine flushings from pregnant wallabies was less than one per cent of the value obtained from day-5 pregnant rabbits. The ability of mouse blastocysts to take up and incorporate [3H]uridine into acidinsoluble material increased threefold in the presence of day-10 endometrial exudates from wallabies. However, this was less than ten percent of the values obtained in the presence of bovine serum albumin. The concentration of calcium in endometrial exudates increased from 23·6 to 45·2 μg/ml during pregnancy; in endometrium it remained at 88·7 μg/g (wet weight) throughout pregnancy, and in plasma it was 53·3 μg/ml. The concentration of zinc in endometrial exudates was 4·5 μg/ml; in endometrium it decreased from 21·8 to 13·3 μg/g (wet weight) during pregnancy and in plasma it was 0·6 μg/ml.

scholarly journals Decreased Expression of the Rat Myometrial Relaxin Receptor (RXFP1) in Late Pregnancy Is Partially Mediated by the Presence of the Conceptus1

2010 ◽  
Vol 83 (5) ◽  
pp. 818-824 ◽  
Author(s):  
Lenka A. Vodstrcil ◽  
Oksana Shynlova ◽  
Jill W. Verlander ◽  
Mary E. Wlodek ◽  
Laura J. Parry
Keyword(s):  
Late Pregnancy ◽  
Relaxin Receptor

scholarly journals Peptide hormone relaxin: from bench to bedside

2018 ◽  
Vol 314 (6) ◽  
pp. R753-R760 ◽  
Author(s):  
Maria Jelinic ◽  
Sarah A. Marshall ◽  
Dennis Stewart ◽  
Elaine Unemori ◽  
Laura J. Parry ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Animal Studies ◽  
Ischemia Reperfusion ◽  
Peptide Hormone ◽  
The Body ◽  
Cervical Ripening ◽  
Matrix Remodeling ◽  
Vitro Fertilization

The peptide hormone relaxin has numerous roles both within and independent of pregnancy and is often thought of as a “pleiotropic hormone.” Relaxin targets several tissues throughout the body, and has many functions associated with extracellular matrix remodeling and the vasculature. This review considers the potential therapeutic applications of relaxin in cervical ripening, in vitro fertilization, preeclampsia, acute heart failure, ischemia-reperfusion, and cirrhosis. We first outline the animal models used in preclinical studies to progress relaxin into clinical trials and then discuss the findings from these studies. In many cases, the positive outcomes from preclinical animal studies were not replicated in human clinical trials. Therefore, the focus of this review is to evaluate the various animal models used to develop relaxin as a potential therapeutic and consider the limitations that must be addressed in future studies. These include the use of human relaxin in animals, duration of relaxin treatment, and the appropriateness of the clinical conditions being considered for relaxin therapy.

Abstract 219: Cardiac Angiogenic Imbalance Leads to Peripartum Cardiomyopathy

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Zolt Arany ◽  
Ian Patten ◽  
Sarosh Rana ◽  
Sajid Shahul ◽  
Glenn Rowe ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Systolic Dysfunction ◽  
Late Pregnancy ◽  
Peripartum Cardiomyopathy ◽  
Late Gestation ◽  
Multiple Gestation ◽  
Plasma Samples ◽  
Fatal Disease ◽  
Vegf Inhibitors ◽  
Circulating Levels

Peri-partum cardiomyopathy (PPCM) is a frequently fatal disease that affects women near delivery, and occurs more frequently in women with pre-eclampsia and/or multiple gestation. The etiology of PPCM, or why it associates with pre-eclampsia, remains unknown. We show here that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-1α, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble Flt1 (sFlt1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by sub-clinical cardiac dysfunction, the extent of which correlates with circulating levels of sFlt1. Exogenous sFlt1 alone caused diastolic dysfunction in wildtype mice, and profound systolic dysfunction in mice lacking cardiac PGC-1α. Finally, plasma samples from women with PPCM contained abnormally high levels of sFlt1. These data strongly suggest that PPCM is in large part a vascular disease, caused by excess anti-angiogenic signaling in the peri-partum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.

Abstract P270: First Trimester Elevation in Circulating Endothelin-1 and Arterial Stiffness are Predictive of Late Pregnancy Preeclampsia

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Alexandria M Betz ◽  
Gary L Pierce ◽  
Donna A Santillan ◽  
Eric J Devor ◽  
Sabrina M Scroggins ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Late Pregnancy ◽  
Fold Increase ◽  
First Trimester ◽  
The Novel ◽  
Pregnancy Hypertension ◽  
Endothelin 1 ◽  
Potent Vasoconstrictor ◽  
Novel Concept ◽  
Nested Case Control

Preeclampsia (PE) is characterized by late pregnancy hypertension and proteinuria. PE causes significant morbidity for the maternal-fetal unit. Circulating endothelin-1 (ET-1), a potent vasoconstrictor, is elevated at the time of diagnosis of human PE. In addition, women with PE demonstrate arterial stiffness as early as the end of the first trimester. However, it is unknown if arterial stiffness is associated with a first trimester elevation in ET-1 and post-delivery placental ET-1. We hypothesized that 1) first trimester plasma ET-1 is elevated and is associated with arterial stiffness in women who develop PE; 2) first trimester ET-1 is predictive of PE; and 3) placental ET-1 is increased in PE. To address these questions, we performed a nested case-control study in women at risk for PE. First trimester plasma ET-1 was measured via ELISA; aortic stiffness and carotid beta-stiffness (CβS) were measured by carotid-femoral pulse-wave velocity (CFPWV) and carotid tonometry/ultrasound, respectively. While the maternal age of controls (n=126; age 30 ± 0.45 years) and PE (n=15; age 31 ± 1.3 years) were similar, the PE group had a higher first trimester BMI (35 ± 3 vs. 29 ± 1 kg/m 2 , p = 0.01), systolic (125 ± 2 vs. 113 ± 1 mmHg, p< 0.01) and diastolic blood pressure (68 ± 2 vs. 60 ± 1 mmHg, p< 0.01) compared with controls. In addition, first trimester plasma ET-1 (2.7 ± 0.4 vs. 2.0 ± 0.2 pg/mL, p < 0.01), CFPWV (7.2 ± 0.5 vs. 6.1 ± 0.2 m/s, p = 0.016), and CβS (8.4 ± 1.9 vs. 6.3 ± 0.3, p = 0.055) were higher in the PE group. Consistent with previous studies, third trimester plasma ET-1 was elevated in the PE group (2.9 ± 1.1 vs. 1.6 ± 0.1 pg/mL, p < 0.01) which paralleled a 2.5 fold increase in placental decidual ET-1 mRNA (p < 0.0001). ROC analyses showed that first trimester plasma ET-1 (AUC=0.71, p < 0.001) and CFPWV (AUC=0.70, p=0.014) were predictive of PE. This study supports the novel concept that elevated ET-1 in preeclampsia begins early in the first trimester and is associated with premature arterial stiffness. Further, these novel data suggest that ET-1 may play an important role in the first trimester prediction and pathogenesis of preeclampsia.

scholarly journals 3134 Organophosphate pesticide exposure during pregnancy, gestational weight gain and long-term postpartum weight retention

2019 ◽  
Vol 3 (s1) ◽  
pp. 50-50
Author(s):  
Linda G Kahn ◽  
Elise M Philips ◽  
Michiel A van den Dries ◽  
Romy Gaillard ◽  
Susana Santos ◽  
...  
Keyword(s):  
Weight Gain ◽  
Pesticide Exposure ◽  
Late Pregnancy ◽  
Fold Increase ◽  
Folic Acid Supplementation ◽  
Weight Retention ◽  
Obese Women ◽  
Gestational Weight ◽  
Pesticide Metabolites ◽  
Postpartum Weight

OBJECTIVES/SPECIFIC AIMS: Little is known about potentially obesogenic endocrine-disruptors’ effects on excessive gestational weight gain (GWG) and postpartum weight retention (PPWR), which increase risk of adverse pregnancy and postnatal outcomes. We explored associations between prenatal organophosphate (OP) pesticide exposure and increased weight both during and after pregnancy. METHODS/STUDY POPULATION: Three dimethyl (DM) and three diethyl (DE) OP metabolites were measured in spot urine samples collected at <18, 18-25, and >25 gestational weeks among 688 participants in the Generation R Study. Metabolite levels were expressed as molar concentration/gram creatinine and log10-transformed. GWG and PPWR were calculated as the difference between weight at each prenatal/postnatal visit or maximum gestational weight and pre-pregnancy weight. In covariate-adjusted regression models we assessed associations of metabolite concentrations at each prenatal visit and, where appropriate, averaged across pregnancy with early-to-mid pregnancy, mid-to-late pregnancy, late pregnancy-to-maximum, and total GWG; insufficient and excessive GWG according to Institute of Medicine guidelines; and long-term PPWR at 6 and 10 years postpartum. Based on OP pesticides’ lipophilicity and association with hypomethylation, we investigated interactions with pre-pregnancy body mass index, periconceptional folic acid supplementation, and breastfeeding duration. RESULTS/ANTICIPATED RESULTS: A 10-fold increase in late pregnancy DE metabolite concentration was associated with 1.34 kg [95% confidence interval: 0.55, 2.12] higher late pregnancy-to-maximum GWG. A 10-fold increase in mean DE metabolite concentration across pregnancy was associated with 2.41 kg [0.62, 4.20] lower PPWR at 6 years. Stratified analysis suggested that the prenatal finding was driven by women with pre-pregnancy BMI ≥25 kg/m2, while the postnatal finding was driven by women with pre-pregnancy BMI <25 kg/m2 and with inadequate folic acid supplementation. We found no associations between OP pesticide metabolites and insufficient or excessive weight gain and no interaction with breastfeeding. DISCUSSION/SIGNIFICANCE OF IMPACT: In this longitudinal analysis, we observed a positive association of OP pesticide metabolites with GWG in late pregnancy among overweight/obese women, potentially reflecting inhibition of OP pesticide detoxification by oxidative stress. Postnatally, under/normal weight women with higher OP pesticide metabolites had lower PPWR, possibly due to better metabolic function and a more healthful diet. These results suggest that there may be a critical period during the late phase of pregnancy when OP pesticide exposure may increase GWG, and this association may be amplified in overweight/obese women. Areas for future research include examination of how the interaction between OP pesticides and polymorphisms of the paraoxonase (PON1) gene, which detoxifies OP pesticides, affect GWG/PPWR; exploration of the interplay among maternal pre-pregnancy BMI, oxidative stress, and PON1 levels; and characterization of the variability of OP pesticides exposure across pregnancy using more frequent repeated urine samples.

The induction of a specific protease for insulin-like growth factor binding protein-3 in the circulation during severe illness

1991 ◽  
Vol 130 (3) ◽  
pp. 469-NP ◽  
Author(s):  
S. C. Davies ◽  
J. A. H. Wass ◽  
R. J. M. Ross ◽  
A. M. Cotterill ◽  
C. R. Buchanan ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Specific Binding ◽  
Nitrogen Retention ◽  
Late Pregnancy ◽  
Severe Illness ◽  
Igf I ◽  
Catabolic State ◽  
Specific Protease ◽  
Circulating Levels ◽  
Igfbp 3

ABSTRACT The insulin-like growth factors (IGF-I and IGF-II) are almost completely bound in the circulation to specific binding proteins (IGFBPs). These IGFBPs appear to play a pivotal role in maintaining circulating levels and modulating the delivery of the IGFs to the tissues. A large proportion of the circulating IGFs are bound with high affinity to one of the binding proteins, IGFBP-3. The mechanism by which these IGFs are transferred from the circulatory pool to the tissue receptors is at present unclear. Recent studies in late pregnancy have demonstrated the presence of specific proteases which may modify the IGFBPs such that their affinities for the IGFs are reduced. In this paper, we have demonstrated the presence of a heat-sensitive cation-dependent proteolytic enzyme specific for IGFBP-3 in the serum of five severely ill patients. The activity of this protease was found to vary in these patients, becoming more apparent during fasting than when studied after commencement of parenteral nutrition, indicating that one of the influencing factors in the activity of this protease is the nutritional intake of the patient. Age- and sex-matched healthy adults were also studied in a similar protocol, but no proteolytic modification of any of the IGFBPs was found in any of the samples examined. As the levels of both IGF-I and IGF-II were found to be low in the patients, the presence of a circulatory protease suggests that this may be an adaptive response to increase the bioavailability of the IGFs and possibly to improve the nitrogen retention and counter the catabolic state in severe illness. Journal of Endocrinology (1991) 130,469–473

scholarly journals Hepatic storage of oligosaccharides and glycolipids in a cat affected with GM1 gangliosidosis

1978 ◽  
Vol 175 (3) ◽  
pp. 945-953 ◽  
Author(s):  
E W Holmes ◽  
J S O'Brien
Keyword(s):  
Periodate Oxidation ◽  
Fold Increase ◽  
Ganglioside Gm1 ◽  
Neutral Glycolipid ◽  
Terminal Position ◽  
Liver Sample ◽  
Gm1 Gangliosidosis ◽  
Glycolipid Fraction ◽  
Wet Weight

1. Glycopeptides and glycolipids were isolated from normal cat liver and liver from a cat affected with GM1 gangliosidosis. 2. Bio-Gel P-6 chromatography of the crude glycopeptide fractions demonstrated three major peaks of hexose-containing compounds that were greatly increased in the mutant liver sample; these peaks contained oligosaccharides that comprised over 2% of the liver wet weight. 3. Two of the major pathological oligosaccharides, GP5 and GP6, were purified by chromatography on charcoal/Celite and Sephadex G-25. Oligosaccharides GP5 and GP6 had apparent mol.wts. of 1800 +/- 200 and 1350+/-200 respectively, and contained galactose, mannose and N-acetylglucosamine in molar proportions of 2.0:3.1:4.1 (GP5) and 1.0:2.2:2.7 (GP6). Periodate oxidation studies demonstrated the presence of galactose in a non-reducing terminal position. 4. The neutral glycolipid fraction from the mutant cat liver has a 1.3-fold increase in hexose content accompanied by an increased concentration of asialo-(ganglioside GM1). 5. There was a 2-fold increase of gangliosides in the mutant cat liver compared with normal cats. Ganglioside GM1 and a compound tentatively identified as N-glycolloyl-(ganglioside GM1) were the major glycolipids accumulated.

Methods for cervical ripening and labour induction in late pregnancy: generic protocol

2009 ◽  
Author(s):  
G Justus Hofmeyr ◽  
Zarko Alfirevic ◽  
Anthony J Kelly ◽  
Josephine Kavanagh ◽  
Jane Thomas ◽  
...  
Keyword(s):  
Late Pregnancy ◽  
Cervical Ripening ◽  
Labour Induction
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