Abnormal extracellular matrix remodelling in the cervix of pregnant relaxin-deficient mice is not associated with reduced matrix metalloproteinase expression or activity

Sarah Marshall, Jonathan T. McGuane, Yu May Soh, Helen Gehring, Emma Simpson, Laura J Parry

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Relaxin regulates cervical extracellular matrix (ECM) remodelling during pregnancy by modifying collagen and other ECM molecules by unknown mechanisms. We hypothesised that abnormal collagen remodelling in the cervix of pregnant relaxin-deficient (Rln1 -/-) mice is due to excessive collagen (Col1a1 and Col3a1) and decreased matrix metalloproteinases (Mmp2, Mmp9, Mmp13 and Mmp7) and oestrogen receptors (Esr1 and Esr2). Quantitative polymerase chain reaction, gelatinase zymography, MMP activity assays and histological staining evaluated changes in ECM in pregnant wildtype (Rln1 +/+) and Rln1 -/- mice. Cervical Col1a1, Col3a1 and total collagen increased in Rln1 -/- mice and were higher at term compared with Rln1 +/+ mice. This was not correlated with a decrease in gelatinase (Mmp2, Mmp9) expression or activity, Mmp7 or Mmp13 expression, which were all significantly higher in Rln1 -/- mice. In late pregnancy, circulating MMP2 and MMP9 were unchanged. Esr1 expression was highest in Rln1 +/+ and Rln1 -/- mice in late pregnancy, coinciding with a decrease in Esr2 in Rln1 +/+ but not Rln1 -/- mice. The relaxin receptor (Rxfp1) decreased slightly in late-pregnant Rln1 +/+ mice, but was significantly higher in Rln1 -/- mice. In summary, relaxin deficiency results in increased cervical collagen in late pregnancy, which is not explained by a reduction in Mmp expression or activity or decreased Rxfp1. However, an imbalance between Esr1 and Esr2 may be involved.

Original languageEnglish
Article numberRD17544
Pages (from-to)1214-1224
Number of pages11
JournalReproduction, Fertility and Development
Volume30
Issue number9
DOIs
Publication statusPublished - 1 Jan 2018
Externally publishedYes

Keywords

  • collagen
  • oestrogen receptor
  • pregnancy
  • rhRLX
  • RXFP1

Cite this

@article{3189b2fc0a9e49d9bf6dc31016048e7b,
title = "Abnormal extracellular matrix remodelling in the cervix of pregnant relaxin-deficient mice is not associated with reduced matrix metalloproteinase expression or activity",
abstract = "Relaxin regulates cervical extracellular matrix (ECM) remodelling during pregnancy by modifying collagen and other ECM molecules by unknown mechanisms. We hypothesised that abnormal collagen remodelling in the cervix of pregnant relaxin-deficient (Rln1 -/-) mice is due to excessive collagen (Col1a1 and Col3a1) and decreased matrix metalloproteinases (Mmp2, Mmp9, Mmp13 and Mmp7) and oestrogen receptors (Esr1 and Esr2). Quantitative polymerase chain reaction, gelatinase zymography, MMP activity assays and histological staining evaluated changes in ECM in pregnant wildtype (Rln1 +/+) and Rln1 -/- mice. Cervical Col1a1, Col3a1 and total collagen increased in Rln1 -/- mice and were higher at term compared with Rln1 +/+ mice. This was not correlated with a decrease in gelatinase (Mmp2, Mmp9) expression or activity, Mmp7 or Mmp13 expression, which were all significantly higher in Rln1 -/- mice. In late pregnancy, circulating MMP2 and MMP9 were unchanged. Esr1 expression was highest in Rln1 +/+ and Rln1 -/- mice in late pregnancy, coinciding with a decrease in Esr2 in Rln1 +/+ but not Rln1 -/- mice. The relaxin receptor (Rxfp1) decreased slightly in late-pregnant Rln1 +/+ mice, but was significantly higher in Rln1 -/- mice. In summary, relaxin deficiency results in increased cervical collagen in late pregnancy, which is not explained by a reduction in Mmp expression or activity or decreased Rxfp1. However, an imbalance between Esr1 and Esr2 may be involved.",
keywords = "collagen, oestrogen receptor, pregnancy, rhRLX, RXFP1",
author = "Sarah Marshall and McGuane, {Jonathan T.} and Soh, {Yu May} and Helen Gehring and Emma Simpson and Parry, {Laura J}",
year = "2018",
month = "1",
day = "1",
doi = "10.1071/RD17544",
language = "English",
volume = "30",
pages = "1214--1224",
journal = "Reproduction, Fertility and Development",
issn = "1031-3613",
publisher = "CSIRO",
number = "9",

}

Abnormal extracellular matrix remodelling in the cervix of pregnant relaxin-deficient mice is not associated with reduced matrix metalloproteinase expression or activity. / Marshall, Sarah; McGuane, Jonathan T.; Soh, Yu May; Gehring, Helen; Simpson, Emma; Parry, Laura J.

In: Reproduction, Fertility and Development, Vol. 30, No. 9, RD17544, 01.01.2018, p. 1214-1224.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Abnormal extracellular matrix remodelling in the cervix of pregnant relaxin-deficient mice is not associated with reduced matrix metalloproteinase expression or activity

AU - Marshall, Sarah

AU - McGuane, Jonathan T.

AU - Soh, Yu May

AU - Gehring, Helen

AU - Simpson, Emma

AU - Parry, Laura J

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Relaxin regulates cervical extracellular matrix (ECM) remodelling during pregnancy by modifying collagen and other ECM molecules by unknown mechanisms. We hypothesised that abnormal collagen remodelling in the cervix of pregnant relaxin-deficient (Rln1 -/-) mice is due to excessive collagen (Col1a1 and Col3a1) and decreased matrix metalloproteinases (Mmp2, Mmp9, Mmp13 and Mmp7) and oestrogen receptors (Esr1 and Esr2). Quantitative polymerase chain reaction, gelatinase zymography, MMP activity assays and histological staining evaluated changes in ECM in pregnant wildtype (Rln1 +/+) and Rln1 -/- mice. Cervical Col1a1, Col3a1 and total collagen increased in Rln1 -/- mice and were higher at term compared with Rln1 +/+ mice. This was not correlated with a decrease in gelatinase (Mmp2, Mmp9) expression or activity, Mmp7 or Mmp13 expression, which were all significantly higher in Rln1 -/- mice. In late pregnancy, circulating MMP2 and MMP9 were unchanged. Esr1 expression was highest in Rln1 +/+ and Rln1 -/- mice in late pregnancy, coinciding with a decrease in Esr2 in Rln1 +/+ but not Rln1 -/- mice. The relaxin receptor (Rxfp1) decreased slightly in late-pregnant Rln1 +/+ mice, but was significantly higher in Rln1 -/- mice. In summary, relaxin deficiency results in increased cervical collagen in late pregnancy, which is not explained by a reduction in Mmp expression or activity or decreased Rxfp1. However, an imbalance between Esr1 and Esr2 may be involved.

AB - Relaxin regulates cervical extracellular matrix (ECM) remodelling during pregnancy by modifying collagen and other ECM molecules by unknown mechanisms. We hypothesised that abnormal collagen remodelling in the cervix of pregnant relaxin-deficient (Rln1 -/-) mice is due to excessive collagen (Col1a1 and Col3a1) and decreased matrix metalloproteinases (Mmp2, Mmp9, Mmp13 and Mmp7) and oestrogen receptors (Esr1 and Esr2). Quantitative polymerase chain reaction, gelatinase zymography, MMP activity assays and histological staining evaluated changes in ECM in pregnant wildtype (Rln1 +/+) and Rln1 -/- mice. Cervical Col1a1, Col3a1 and total collagen increased in Rln1 -/- mice and were higher at term compared with Rln1 +/+ mice. This was not correlated with a decrease in gelatinase (Mmp2, Mmp9) expression or activity, Mmp7 or Mmp13 expression, which were all significantly higher in Rln1 -/- mice. In late pregnancy, circulating MMP2 and MMP9 were unchanged. Esr1 expression was highest in Rln1 +/+ and Rln1 -/- mice in late pregnancy, coinciding with a decrease in Esr2 in Rln1 +/+ but not Rln1 -/- mice. The relaxin receptor (Rxfp1) decreased slightly in late-pregnant Rln1 +/+ mice, but was significantly higher in Rln1 -/- mice. In summary, relaxin deficiency results in increased cervical collagen in late pregnancy, which is not explained by a reduction in Mmp expression or activity or decreased Rxfp1. However, an imbalance between Esr1 and Esr2 may be involved.

KW - collagen

KW - oestrogen receptor

KW - pregnancy

KW - rhRLX

KW - RXFP1

UR - http://www.scopus.com/inward/record.url?scp=85049246967&partnerID=8YFLogxK

U2 - 10.1071/RD17544

DO - 10.1071/RD17544

M3 - Article

VL - 30

SP - 1214

EP - 1224

JO - Reproduction, Fertility and Development

JF - Reproduction, Fertility and Development

SN - 1031-3613

IS - 9

M1 - RD17544

ER -