Document Detail


Increased MMPs expression and decreased contraction in the rat myometrium during pregnancy and in response to prolonged stretch and sex hormones.
MedLine Citation:
PMID:  22496348     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Normal pregnancy is associated with uterine relaxation to accommodate the stretch imposed by the growing fetus; however, the mechanisms underlying the relationship between pregnancy-associated uterine stretch and uterine relaxation are unclear. We hypothesized that increased uterine stretch during pregnancy is associated with upregulation of matrix metalloproteinases (MMPs), which in turn cause inhibition of myometrium contraction and promote uterine relaxation. Uteri from virgin, midpregnant (day 12), and late-pregnant rats (day 19) were isolated, and myometrium strips were prepared for measurement of isometric contraction and MMP expression and activity using RT-PCR, Western blot analysis, and gelatin zymography. Oxytocin caused concentration-dependent contraction of myometrium strips that was reduced in mid- and late-pregnant rats compared with virgin rats. Pretreatment with the MMP inhibitors SB-3CT (MMP-2/MMP-9 Inhibitor IV), BB-94 (batimastat), or Ro-28-2653 (cipemastat) enhanced contraction in myometrium of pregnant rats. RT-PCR, Western blot analysis, and gelatin zymography demonstrated increased mRNA expression, protein amount, and activity of MMP-2 and MMP-9 in myometrium of late-pregnant>midpregnant>virgin rats. Prolonged stretch of myometrium strips of virgin rats under 8 g basal tension for 18 h was associated with reduced contraction and enhanced expression and activity of MMP-2 and MMP-9, which were reversed by MMP inhibitors. Concomitant treatment of stretched myometrium of virgin rats with 17β-estradiol (E2), progesterone (P4), or E2+P4 was associated with further reduction in contraction and increased MMP expression and activity. MMP-2 and MMP-9 caused significant reduction of oxytocin-induced contraction of myometrium of virgin rat. Thus, normal pregnancy is associated with reduced myometrium contraction and increased MMPs expression and activity. The results are consistent with the possibility that myometrium stretch and concomitant increase in sex hormones during pregnancy are associated with increased expression/activity of specific MMPs, which in turn inhibit uterine contraction and promote uterine relaxation.
Authors:
Zongzhi Yin; Alaa A Sada; Ossama M Reslan; Neha Narula; Raouf A Khalil
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-10
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  303     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-09-10     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E55-70     Citation Subset:  IM    
Affiliation:
Vascular Surgery Research Laboratory, Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Boston, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Enzyme Induction* / drug effects
Estradiol / metabolism*
Female
Matrix Metalloproteinase 2 / genetics,  metabolism*
Matrix Metalloproteinase 9 / genetics,  metabolism*
Matrix Metalloproteinase Inhibitors
Muscle Relaxation / drug effects
Muscle Tonus / drug effects
Myography
Myometrium / drug effects,  enzymology*,  metabolism
Osmolar Concentration
Oxytocin / metabolism
Physical Stimulation
Pregnancy
Progesterone / metabolism*
Protease Inhibitors / pharmacology
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Uterine Contraction* / drug effects
Grant Support
ID/Acronym/Agency:
HD-60702/HD/NICHD NIH HHS; HL-65998/HL/NHLBI NIH HHS; HL-98724/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Matrix Metalloproteinase Inhibitors; 0/Protease Inhibitors; 0/RNA, Messenger; 50-28-2/Estradiol; 50-56-6/Oxytocin; 57-83-0/Progesterone; EC 3.4.24.-/Mmp9 protein, rat; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.24/Mmp2 protein, rat; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

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